Cannabis and the lung.

The use of cannabis is embedded within many societies, mostly used by the young and widely perceived to be safe. Increasing concern regarding the potential for cannabis to cause mental health effects has dominated cannabis research and the potential adverse respiratory effects have received relatively little attention. Studies on cannabis are challenging and subject to confounding by concomitant use of tobacco and other social factors, and while many of the studies referred to in this review are beset by the difficulties inherent in undertaking epidemiological research of the effects of cannabis, there is an emerging concern among many chest physicians who would suggest that habitual smoking of cannabis may contribute to the development of chronic obstructive pulmonary disease, pneumothorax and respiratory infections, including tuberculosis. Special attention should be given to the risk of lung cancer, particularly as biological plausibility may precede epidemiology.

Tobacco smoking and chewing, alcohol drinking and lung cancer risk among men in southern India.

In India, lung cancer is one of the most common and lethal cancers, and tobacco smoking remains its most important etiologic factors. The objective of our study is to examine the effects of different tobacco consumption forms, including smoking and chewing, on lung cancer risk of men in southern India, especially to compare the effects of bidi smoking to cigarette smoking on lung carcinogenesis. We also evaluated the possible role of Indian alcohol beverages and non-Indian alcohol beverages on lung carcinogenesis. We conducted a case-control study in Chennai and Trivandrum. In total, 778 lung cancer cases and 3,430 controls, including 1,503 cancer controls and 1,927 healthy controls, were recruited. The effects of cigarette, bidi smoking, chewing and alcohol drinking on the risk of lung cancer were estimated from unconditional multivariate logistic regression. We also applied the generalized additive model (GAM) with locally-weighted running-line smoothers (loess) to find the most plausible curve for the dose-response relationship. The results from GAM suggest a plateau after 35 years of smoking or 10 cigarette-equivalent pack-years for both cigarette and bidi. The OR is 4.54 (95%CI=2.96-6.95) and 6.45 (95%CI=4.38-9.50) for more than 30 years of cigarette-only and bidi-only smoking, respectively, and 6.87 (95%CI=4.62-10.2) and 10.7 (95%CI=5.82-19.6) for more than 12 weighted cumulative cigarette-only and bidi-only consumption, respectively. The lung cancer risk of former cigarette smokers drops down more quickly after quitting smoking compared to former bidi smokers. There is no evidence for the effect of chewing and lung cancer risk nor clear evidence of an effect of overall alcohol drinking among never-smokers, although Indian alcohol drinking seemed to remain associated with lung cancer risk under limited power (OR=2.67, 95%CI=1.02-7.02). Bidi smoking seems to have a stronger carcinogenic effect than cigarette smoking: this difference holds no matter which aspect of smoking was considered. Copyright 2003 Wiley-Liss, Inc.

Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates.

Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.

It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco

The Family Smoking Prevention and Tobacco Control Act gives the Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International Agency for Research on Cancer. NNK and NNN are present in the tobacco of virtually all marketed cigarettes; levels in cigarette smoke are directly proportional to the amounts in tobacco. The NNK metabolite NNAL, itself a strong carcinogen, is present in the urine of smokers and non-smokers exposed to secondhand smoke. Some of the highest levels of NNK and NNN are found in U.S. products. It is well established that factors such as choice of tobacco blend, agricultural conditions, and processing methods influence levels of NNK and NNN in cigarette tobacco and cigarette smoke. Therefore, it is time to control these factors and produce cigarettes with 100 ppb or less each of NNK and NNN in tobacco, which would result in an approximate 15-20 fold reduction of these carcinogens in the mainstream smoke of popular cigarettes sold in the United States.

Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study.

Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.

Semen quality of male idiopathic infertile smokers and nonsmokers: an ultrastructural study.

This retrospective study was aimed at evaluating the effects of cigarette consumption on semen parameters in a group of men with idiopathic infertility. The semen quality of 2 groups of men with idiopathic infertility, smokers (n = 118) and nonsmokers (n = 153), were compared. Conventional semen analysis was performed and sperm morphology was assessed by transmission electron microscopy (TEM). TEM data were elaborated by means of a mathematical formula based on a Bayesian technique able to furnish a fertility index (FI), and the percentages of sperm apoptosis, necrosis, and immaturity. Values of normality recommended by World Health Organization guidelines were used as a control for conventional semen analysis, and values from sperm of 25 men of proven fertility were used for TEM indices. Infertile smoker and nonsmoker patients showed similar sperm parameters, although sperm motility and TEM analysis values in both groups were significantly impaired compared with controls. Smoker patients were then classified as mild (>or=1 and <or=10 cigarettes/d), moderate (>10 and <20 cigarettes/day), or heavy smokers (>or=20 cigarettes/d). Sperm concentration and FI were significantly (P < .05) different among the 3 considered smoker classes. Comparing the pairs of smoker classes, sperm concentration and FI in heavy smokers were significantly lower (P < .05) than that observed in mild smoker and nonsmoker groups. Although semen quality in males with idiopathic infertility seems not to be dramatically affected by cigarette consumption, heavy smokers show significantly lower sperm concentration and FI: another strong reason to stop smoking.

Exposure to beta-carbolines norharman and harman.

The aromatic beta-carbolines norharman and harman have been implicated in a number of human diseases including Parkinson's disease, tremor, addiction and cancer. It has been shown that these compounds are normal body constituents formed endogenously but external sources have been identified. Here, we summarise literature data on levels of norharman and harman in fried meat and fish, meat extracts, alcoholic drinks, and coffee brews. Other sources include edible and medicinal plants but tobacco smoke has been identified as a major source. Exposure levels from these different dietary sources are estimated to a maximum of 4 microg norharman per kg body weight (bw) per day and 1 microg harman per kg bw per day. Exposure via tobacco smoke depends on smoking habits and type of cigarettes but can be estimated to 1.1 microg/kg bw for norharman and 0.6 microg/kg bw for harman per package of cigarettes smoked. Studies on toxicokinetics indicate that inhalative exposure leads to a rapid increase in plasma levels and high bioavailability of norharman and harman. Oral bioavailability is lower but there are indications that sublingual absorption may increase dietary uptake of beta-carbolines. Endogenous formation can be estimated to be 50-100 ng/kg bw per day for norharman and about 20 ng/kg bw per day for harman but these rates may increase with high intake of precursors. Biomarker studies on plasma levels of beta-carbolines reported on elevated levels of norharman, harman or both in diseased patients, alcoholics and following tobacco smoking or consumption of beta-carboline-containing food. Cigarette smoking has been identified as major influence but dietary exposure may contribute to exposure.

Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health

Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.

Smoking and lung cancer risk in American and Japanese men: an international case-control study.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

IMPACT OF BARBECUED MEAT CONSUMED IN PREGNANCY ON BIRTH OUTCOMES ACCOUNTING FOR PERSONAL PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS. BIRTH COHORT STUDY IN POLAND

We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes. The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS). The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period. In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.

Cigarette smoke radioactivity and lung cancer risk.

INTRODUCTION: To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers. METHODS: Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998. RESULTS: The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential "cancerous growth" in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant "nicotine kick" sensation. CONCLUSIONS: The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.

CANNABIS USE AND RISK OF LUNG CANCER: A CASE-CONTROL STUDY

Aim: To determine the risk of lung cancer associated with cannabis smoking. Methods: A case-control study of lung cancer in adults ≤55 years of age was conducted in eight district health boards in New Zealand. Cases were identified from the New Zealand Cancer Registry and hospital databases. Controls were randomly selected from the electoral roll, with frequency matching to cases in 5-year age groups and district health boards. Interviewer administered questionnaires were used to assess possible risk factors including cannabis use. The relative risk of lung cancer associated with cannabis smoking was estimated by logistic regression. Results: There were 79 cases of lung cancer and 324 controls. The risk of lung cancer increased 8% (95% CI 2% to 15%) for each joint-year of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 5% to 9%) for each pack-year of cigarette smoking, after adjustment for confounding variables including cannabis smoking. The highest tertile of cannabis use was associated with an increased risk of lung cancer RR=5.7 (95% CI 1.5 to 21.6), after adjustment for confounding variables including cigarette smoking. Conclusions: Long term cannabis use increases the risk of lung cancer in young adults.

Thirdhand cigarette smoke in an experimental chamber: evidence of surface deposition of nicotine, nitrosamines and polycyclic aromatic hydrocarbons...

BACKGROUND: A growing body of evidence shows that secondhand cigarette smoke undergoes numerous chemical changes after it is released into the air: it can adsorb to indoor surfaces, desorb back into the air and undergo chemical changes as it ages. OBJECTIVES: To test the effects of aging on the concentration of polycyclic aromatic hydrocarbons (PAHs), nicotine and tobacco-specific nitrosamines in cigarette smoke. METHODS: We generated sidestream and mainstream cigarette smoke with a smoking machine, diluted it with conditioned filtered air, and passed it through a 6 m(3) flow reactor with air exchange rates that matched normal residential air exchange rates. We tested the effects of 60 min aging on the concentration of 16 PAHs, nicotine, cotinine and tobacco-specific nitrosamines. We also measured sorption and deposition of nicotine, cotinine and tobacco-specific nitrosamines on materials placed within the flow reactor. RESULTS: We observed mass losses of 62% for PAHs, 72%, for nicotine, 79% for N-nitrosonornicotine and 80% for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Extraction of cotton cloth exposed to smoke yielded nicotine and NNK. The ratio of NNK:nicotine on the exposed cloth was 10-fold higher than that in aerosol samples. CONCLUSIONS: Our data suggest that the majority of the PAHs, nicotine, cotinine and tobacco-specific nitrosamines that are released during smoking in homes and public places deposit on room surfaces. These data give an estimate of the potential for accumulation of carcinogens in thirdhand cigarette smoke. Exposure to PAHs and tobacco-specific nitrosamines, through dermal absorption and inhalation of contaminated dust, may contribute to smoking-attributable morbidity and mortality.

Physician smoking status, attitudes toward smoking, and cessation advice to patients: an international survey.

OBJECTIVE: The smoking status of physicians can impact interactions with patients about smoking. The 'Smoking: The Opinions of Physicians' (STOP) survey examined whether an association existed between physician smoking status and beliefs about smoking and cessation and a physician's clinical interactions with patients relevant to smoking cessation, and perceptions of barriers to assisting with quitting. METHODS: General and family practitioners across 16 countries were surveyed via telephone or face-to-face interviews using a convenience-sample methodology. Physician smoking status was self-reported. RESULTS: Of 4473 physicians invited, 2836 (63%) participated in the survey, 1200 (42%) of whom were smokers. Significantly fewer smoking than non-smoking physicians volunteered that smoking was a harmful activity (64% vs 77%; P<0.001). More non-smokers agreed that smoking cessation was the single biggest step to improving health (88% vs 82%; P<0.001) and discussed smoking at every visit (45% vs 34%; P<0.001). Although more non-smoking physicians identified willpower (37% vs 32%; P<0.001) and lack of interest (28% vs 22%; P<0.001) as barriers to quitting, more smoking physicians saw stress as a barrier (16% vs 10%; P<0.001). CONCLUSION: Smoking physicians are less likely to initiate cessation interventions. PRACTICE IMPLICATIONS: There is a need for specific strategies to encourage smoking physicians to quit, and to motivate all practitioners to adopt systematic approaches to assisting with smoking cessation.

Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice.

Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects. Copyright © 2010 Elsevier Ltd. All rights reserved.

Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction.

Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in monoamine oxidase (MAO) activity, which reverts to control level when they quit smoking. The observed decrease in MAO activity in smokers is presumably due to their exposure to tobacco constituents that possess MAO-inhibiting properties. The inhibition of MAO activity seems, however, not to be a unique feature of tobacco smoking as subjects with Type II alcoholism have been reported to show a similar decrease in MAO activity that reverses when they cease to use alcohol. The present review summarizes the data on MAO-inhibiting tobacco constituents and explains that the decrease in MAO activity observed in alcoholics is probably due to concomitant tobacco use. It is concluded that the inhibition of MAO by constituents contained in tobacco and tobacco smoke, enhances the addiction induced by tobacco smoking.

Exposure to nitrosamines in thirdhand tobacco smoke increases cancer risk in non-smokers.

In addition to passive inhalation, non-smokers, and especially children, are exposed to residual tobacco smoke gases and particles that are deposited to surfaces and dust, known as thirdhand smoke (THS). However, until now the potential cancer risks of this pathway of exposure have been highly uncertain and not considered in public health policy. In this study, we estimate for the first time the potential cancer risk by age group through non-dietary ingestion and dermal exposure to carcinogen N-nitrosamines and tobacco-specific nitrosamines (TSNAs) measured in house dust samples. Using a highly sensitive and selective analytical approach we have determined the presence of nicotine, eight N-nitrosamines and five tobacco-specific nitrosamines in forty-six settled dust samples from homes occupied by both smokers and non-smokers. Using observations of house dust composition, we have estimated the cancer risk by applying the most recent official toxicological information. Calculated cancer risks through exposure to the observed levels of TSNAs at an early life stage (1 to 6years old) exceeded the upper-bound risk recommended by the USEPA in 77% of smokers' and 64% of non-smokers' homes. The maximum risk from exposure to all nitrosamines measured in a smoker occupied home was one excess cancer case per one thousand population exposed. The results presented here highlight the potentially severe long-term consequences of THS exposure, particularly to children, and give strong evidence of its potential health risk and, therefore, they should be considered when developing future environmental and health policies. Copyright © 2014 Elsevier Ltd. All rights reserved.

How does physician advice influence patient behavior? Evidence for a priming effect.

OBJECTIVE: To explore a potential "priming effect" of physician advice on patient responses to behavioral change interventions. DESIGN: Randomized controlled trial with a 3-month follow-up. SETTING: Four community-based group family medicine clinics in southeastern Missouri. PARTICIPANTS: Adult patients (N = 915). INTERVENTIONS: Printed educational materials designed to encourage patients to quit smoking, eat less fat, and increase physical activity. MAIN OUTCOME MEASURES: Recall, rating, and use of the educational materials; changes in smoking behavior, dietary fat consumption, and physical activity. RESULTS: Patients who received physician advice to quit smoking, eat less fat, or get more exercise prior to receiving intervention materials on the same topic were more likely to remember the materials, show them to others, and perceive the materials as applying to them specifically. They were also more likely to report trying to quit smoking (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 0.95-2.40), quitting for at least 24 hours (OR = 1.85, 95% CI = 1.02-3.34), and making some changes in diet (OR = 1.35, 95% CI = 1.00-1.84) and physical activity (OR = 1.51, 95% CI = 0.95-2.40). CONCLUSIONS: Findings support an integrated model of disease prevention in which physician advice is a catalyst for change and is supported by a coordinated system of information and activities that can provide the depth of detail and individualization necessary for sustained behavioral change.

Cadmium intake and systemic exposure in postmenopausal women and age-matched men who smoke cigarettes.

Mean blood cadmium (B-Cd) concentrations are two- to threefold higher in smokers than in nonsmokers. The basis for this phenomenon is not well understood. We conducted a detailed, multifaceted study of cadmium exposure in smokers. Groups were older smokers (62±4 years, n = 25, 20% male) and nonsmokers (62±3 years, n = 16, 31% male). Each subject's cigarettes were machine smoked, generating individually paired measures of inhaled cadmium (I-Cd) versus B-Cd; I-Cd and B-Cd were each evaluated three times, at monthly intervals. Urine cadmium (U-Cd) was analyzed for comparison. In four smokers, a duplicate-diet study was conducted, along with a kinetic study of plasma cadmium versus B-Cd. Female smokers had a mean B-Cd of 1.21ng Cd/ml, with a nearly 10-fold range (0.29-2.74ng Cd/ml); nonsmokers had a lower mean B-Cd, 0.35ng Cd/ml (p < 0.05), and narrower range (0.20-0.61ng Cd/ml). Means and ranges for males were similar. Estimates of cadmium amounts inhaled daily for our subjects smoking ≥ 20 cigarettes/day were far less than the 15 µg Cd reported to be ingested daily via diet. This I-Cd amount was too low to alone explain the 3.5-fold elevation of B-Cd in our smokers, even assuming greater cadmium absorption via lungs than gastrointestinal tract; cadmium accumulated in smokers' lungs may provide the added cadmium. Finally, B-Cd appeared to be linearly related to I-Cd values in 75% of smokers, whereas 25% had far higher B-Cd, implying a possible heterogeneity among smokers regarding circulating cadmium concentrations and potentially cadmium toxicity.

Relative exposure to beta-carbolines norharman and harman from foods and tobacco smoke.

Norharman and harman are two heterocyclic beta-carboline (9H-pyrido[3,4-b]indole) alkaloids with biological and potential toxicological activity that appear in foodstuffs and environmental sources. To assess the occurrence and distribution of these compounds and to estimate the exposure levels based on the detected amounts, numerous samples of foodstuffs and cigarette smoke were analysed by solid-phase extraction and high-performance liquid chromatography-fluorescence. The levels found of beta-carbolines were highly variable. Low processed foodstuffs (i.e. milk, yoghurt, uncooked meats and fish) did not contain norharman and harman above the detection limit. Others, however, contained relatively high concentrations (at the tens of ng g(-1) or microg l(-1) level) depending on the processing conditions as, for example, 'well-done' cooked meat and fish. The highest amounts of norharman and harman were found in brewed coffee (29-207 microg l(-1)), sauces (soy sauce and Tabasco, among others; 4-252 microg l(-1)), 'well done' cooked meat and fish (57-160 ng g(-1)), toasted bread (42-160 ng g(-1)), and fermented alcoholic beverages (n.d.-41 mug l(-1)). beta-Carbolines also occurred in a high amount in the mainstream of cigarette smoke (207-2780 ng/cigarette), which is an important contributor to daily exposure to these compounds. Based on these results, it is concluded that the daily exposure to beta-carbolines in humans might be from tens to hundreds of micrograms, with cigarette smoke, coffee, certain seasonings, cooked foods and alcoholic beverages, in this order, being the major contributors. Many other foodstuffs might also contribute with minor amounts of norharman and harman. Foods and tobacco smoke might be potential contributors to the reported endogenous presence of beta-carbolines in humans.

Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium

Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.

Understanding tobacco smoke carcinogen NNK and lung tumorigenesis.

The deleterious effects of tumor-promoting tobacco carcinogen, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine ketone) have undoubtedly been stipulated. Though many tobacco agents play a part in the development of lung tumors, the potent effects of NNK remain unmatched. It is therefore critical to distinguish the variety of cofactors involved in NNK-mediated pathogenesis, and the unique pathways necessary for successful cellular biotransformation. Current reviews have consistently identified the strengths of NNK and prospective tumor capabilities. Others have delineated specific cellular factors mediating NNK and lung tumors, and have identified metabolic and signaling pathways largely responsible for NNK activation and tumorigenic initiation. Unique to this review is that it summarizes the extensive network of cofactors and cellular mechanisms that promote NNK-specific lung tumorigenesis. As such, it displays a fuller, more comprehensive overview, bringing us one step closer to understanding the fatal consequences of NNK, thus, discovering new avenues that successfully break the cycle of NNK-mediated lung carcinogenesis.

Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH–AARP Cohort

The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH–AARP Diet and Health Study (1995–2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked ≤1 or >1 pack/day and for current smokers who smoked ≤1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia.

Polycyclic aromatic hydrocarbons in smoked food products and commercial liquid smoke flavourings.

Smoked foods including turkey, pork, chicken, beef and fish products were screened for the presence of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons (PAHs). Eighteen commercial liquid smoke flavourings and seasonings were also analysed. Total PAH concentrations in smoked meat products ranged from 2.6 micrograms/kg in a cooked ham sample to 29.8 micrograms/kg in grilled pork chops, while those in fish products ranged from 9.3 micrograms/kg in smoked shrimp to 86.6 micrograms/kg in smoked salmon. Total concentrations of the carcinogenic PAHs (benzo[a]anthracene, benzo[b]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, and indeno[1,2,3-c,d]pyrene) ranged from non-detectable in several meat products to 7.4 micrograms/kg in grilled pork chops, and from 0.2 micrograms/kg in trout to 16.0 micrograms/kg in salmon. In liquid smoke flavourings and seasonings, total PAH concentrations ranged from 6.3 to 43.7 micrograms/kg, with the carcinogenic PAHs ranging from 0.3 to 10.2 micrograms/kg.

Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats.

Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.

Quantification of the co-mutagenic beta-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods.

Co-mutagenic beta-carbolines, such as norharman and harman, were quantified in mainstream and sidestream smoke condensates of six Japanese brands of cigarettes, and also in 13 kinds of cooked foods, using a combination of blue cotton treatment and HPLC. Norharman and harman were detected in all the cigarette smoke condensate samples. Their levels in the mainstream smoke case were 900-4240 ng per cigarette for norharman, and 360-2240 ng for harman, and in sidestream smoke, 4130-8990 ng for norharman and 2100-3000 ng for harman. These beta-carbolines were also found to be present in all the cooked food samples, at levels of 2.39-795 ng for norharman and 0.62-377 ng for harman per gram of cooked food. The observed concentrations are much higher than those found for mutagenic and carcinogenic heterocyclic amines (HCAs), suggesting that humans are exposed to norharman and harman in daily life to a larger extent than to HCAs.

Chronic intake of potato chips in humans increases the production of reactive oxygen radicals by leukocytes and increases plasma C-reactive protein...

BACKGROUND: Relatively high concentrations of acrylamide in commonly ingested food products, such as French fries, potato chips, or cereals, may constitute a potential risk to human health. OBJECTIVE: The objective of this pilot study was to investigate the possible connection between chronic ingestion of acrylamide-containing potato chips and oxidative stress or inflammation. DESIGN: Fourteen healthy volunteers (mean age: 35 y; 8 women and 6 smokers of >20 cigarettes/d) were given 160 g of potato chips containing 157 microg [corrected] acrylamide daily for 4 wk. RESULTS: An increase in acrylamide-hemoglobin adducts in blood was found in all the study subjects, with a mean of 43.1 pmol x L(-1) x g(-1) hemoglobin (range: 27-76; P < 0.01) in nonsmokers and 59.0 pmol x L(-1) x g(-1) hemoglobin (range: 43-132; P < 0.05) in smokers. Concurrently, a significant increase (P < 0.01) in the oxidized LDL, high-sensitivity interleukin-6, high-sensitivity C-reactive protein, and gamma-glutamyltransferase concentrations was observed in both smokers and nonsmokers. A significant increase in reactive oxygen radical production by monocytes, lymphocytes, and granulocytes and an increase in CD14 expression in macrophages (P < 0.001) were found after intake of potato chips. Twenty-eight days from the discontinuation of the experiment, the variables under study decreased to some extent. It has been shown also that acrylamide increases the production of reactive oxygen species in isolated human monocyte-macrophages in vitro and decreases the cellular glutathione concentration. CONCLUSION: These novel findings seem to indicate that chronic ingestion of acrylamide-containing products induces a proinflammatory state, a risk factor for progression of atherosclerosis.

Male reproductive organs are at risk from environmental hazards

Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction, infertility, cryptorchidism, hypospadias and testicular cancer. Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However, the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation, radiant heat and a number of known toxicants. So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane, ethylendibromide and DDT/DDE, some heavy metals as inorganic lead and mercury) and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures, but millions of workers in less affluent countries are at risk from reproductive toxicants. New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world. For other toxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates, bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones. Finally, there are data indicating a particular vulnerability of the fetal testis to toxicants—for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.

4. Chronic pancreatitis and pancreatic cancer, lifestyle-related diseases.

In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.

The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?

Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.

Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli.

OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.

Associations of dietary dark-green and deep-yellow vegetables and fruits with cervical intraepithelial neoplasia: modification by smoking.

Smoking has been positively and fruit and vegetable intake has been negatively associated with cervical cancer, the second most common cancer among women worldwide. However, a lower consumption of fruits and reduced serum carotenoids have been observed among smokers. It is not known whether the smoking effect on the risk of cervical neoplasia is modified by a low intake of fruits and vegetables. The present study examined the combined effects of tobacco smoking and diet using a validated FFQ and serum carotenoid and tocopherol levels on cervical intraepithelial neoplasia grade 3 (CIN3) risk in a hospital-based case-control study conducted in São Paulo, Brazil, between 2003 and 2005. The sample comprised 231 incident, histologically confirmed cases of CIN3 and 453 controls. A low intake ( ≤ 39 g) of dark-green and deep-yellow vegetables and fruits without tobacco smoking had a lesser effect on CIN3 (OR 1·14; 95 % CI 0·49, 2·65) than among smokers with higher intake ( ≥ 40 g; OR 1·83; 95 % CI 0·73, 4·62) after adjusting for confounders. The OR for the joint exposure of tobacco smoking and low intake of vegetables and fruits was greater (3·86; 95 % CI 1·74, 8·57; P for trend < 0·001) compared with non-smokers with higher intake after adjusting for confounding variables and human papillomavirus status. Similar results were observed for total fruit, serum total carotene (including β-, α- and γ-carotene) and tocopherols. These findings suggest that the effect of nutritional factors on CIN3 is modified by smoking.

Effect of turmeric on urinary mutagens in smokers.

Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.

Ten years of life: Is it a matter of choice?

BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.

Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.

Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens

Induction of phase 2 detoxication enzymes [e.g., glutathione transferases, epoxide hydrolase, NAD(P)H: quinone reductase, and glucuronosyltransferases] is a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity of electrophiles and reactive forms of oxygen. Since consumption of large quantities of fruit and vegetables is associated with a striking reduction in the risk of developing a variety of malignancies, it is of interest that a number of edible plants contain substantial quantities of compounds that regulate mammalian enzymes of xenobiotic metabolism. Thus, edible plants belonging to the family Cruciferae and genus Brassica (e.g., broccoli and cauliflower) contain substantial quantities of isothiocyanates (mostly in the form of their glucosinolate precursors) some of which (e.g., sulforaphane or 4-methylsulfinylbutyl isothiocyanate) are very potent inducers of phase 2 enzymes. Unexpectedly, 3-day-old sprouts of cultivars of certain crucifers including broccoli and cauliflower contain 10–100 times higher levels of glucoraphanin (the glucosinolate of sulforaphane) than do the corresponding mature plants. Glucosinolates and isothiocyanates can be efficiently extracted from plants, without hydrolysis of glucosinolates by myrosinase, by homogenization in a mixture of equal volumes of dimethyl sulfoxide, dimethylformamide, and acetonitrile at −50°C. Extracts of 3-day-old broccoli sprouts (containing either glucoraphanin or sulforaphane as the principal enzyme inducer) were highly effective in reducing the incidence, multiplicity, and rate of development of mammary tumors in dimethylbenz(a)anthracene-treated rats. Notably, sprouts of many broccoli cultivars contain negligible quantities of indole glucosinolates, which predominate in the mature vegetable and may give rise to degradation products (e.g., indole-3-carbinol) that can enhance tumorigenesis. Hence, small quantities of crucifer sprouts may protect against the risk of cancer as effectively as much larger quantities of mature vegetables of the same variety.

Diet and nutrients are contributing factors that influence blood cadmium levels.

Studies suggested the intake of Cd from diet can be approximately equivalent to that from smoking. Moreover, a mutual metabolic influence between Cd and nutrients has been reported. The purpose of this study was to evaluate the relationship between blood cadmium concentration (BCdC) and food consumption, nutrients intake (Ca, Fe, Zn, vitamin C, and vitamin D), tobacco smoking, and some other variables (age, body mass index, and residence) in 243 adults living in the Italian island of Sardinia (Sassari Province). Specifically, we hypothesized that offal consumption contributes to Cd intakes and blood levels. The BCdC was quantified by graphite furnace atomic absorption spectrometry, and information on personal data was collected through questionnaires. Smoke significantly contributed to the BCdC (P < .001). Nonsmoker subjects who eat offal showed significantly higher BCdC (P = .04). Moreover, slightly higher BCdCs were also observed in nonsmoker subjects who eat rice, fish, and bread. The BCdC positively correlated with age of subjects (r = 0.144; P = .025) and offal daily intake in nonsmokers (r = 0.393; P < .001). The intake of Ca was negatively correlated (r = -0.281; P = .001) with the BCdC in females. The multiple linear regression analysis showed smoking > consumption of offal > body mass index ≈ age as the most important risk factors for the BCdC in the selected population. Copyright © 2011 Elsevier Inc. All rights reserved.

Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions.

In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 μg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 μg m(-3)) and Western (21.47 ± 11.44 μg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 μg m(-3)), followed by Western (0.86 ± 1.43 μg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 μg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6). Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study

Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.

Long-term Use of β-Carotene, Retinol, Lycopene, and Lutein Supplements and Lung Cancer Risk: Results From the VITamins And Lifestyle (VITAL) Study

High-dose β-carotene supplementation in high-risk persons has been linked to increased lung cancer risk in clinical trials; whether effects are similar in the general population is unclear. The authors examined associations of supplemental β-carotene, retinol, vitamin A, lutein, and lycopene with lung cancer risk among participants, aged 50–76 years, in the VITamins And Lifestyle (VITAL) cohort Study in Washington State. In 2000–2002, eligible persons (n = 77,126) completed a 24-page baseline questionnaire, including detailed questions about supplement use (duration, frequency, dose) during the previous 10 years from multivitamins and individual supplements/mixtures. Incident lung cancers (n = 521) through December 2005 were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Longer duration of use of individual β-carotene, retinol, and lutein supplements (but not total 10-year average dose) was associated with statistically significantly elevated risk of total lung cancer and histologic cell types; for example, hazard ratio = 2.02, 95% confidence interval: 1.28, 3.17 for individual supplemental lutein with total lung cancer and hazard ratio = 3.22, 95% confidence interval: 1.29, 8.07 for individual β-carotene with small-cell lung cancer for >4 years versus no use. There was little evidence for effect modification by gender or smoking status. Long-term use of individual β-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.

Healthy lifestyle behaviors and all-cause mortality among adults in the United States.

OBJECTIVE: To examine the links between three fundamental healthy lifestyle behaviors (not smoking, healthy diet, and adequate physical activity) and all-cause mortality in a national sample of adults in the United States. METHOD: We used data from 8375 U.S. participants aged ≥ 20 years of the National Health and Nutrition Examination Survey 1999-2002 who were followed through 2006. RESULTS: During a mean follow-up of 5.7 years, 745 deaths occurred. Compared with their counterparts, the risk for all-cause mortality was reduced by 56% (95% confidence interval [CI]: 35%-70%) among adults who were nonsmokers, 47% (95% CI: 36%, 57%) among adults who were physically active, and 26% (95% CI: 4%, 42%) among adults who consumed a healthy diet. Compared with participants who had no healthy behaviors, the risk decreased progressively as the number of healthy behaviors increased. Adjusted hazard ratios and 95% confidence interval were 0.60 (0.38, 0.95), 0.45 (0.30, 0.67), and 0.18 (0.11, 0.29) for 1, 2, and 3 healthy behaviors, respectively. CONCLUSION: Adults who do not smoke, consume a healthy diet, and engage in sufficient physical activity can substantially reduce their risk for early death. Published by Elsevier Inc.

Coffee and its consumption: benefits and risks.

Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers. © Taylor and Francis Group, LLC

A modest proposal for a longitudinal study of dementia prevention (with apologies to Jonathan Swift, 1729).

Many studies have documented the role of risk and protective factors for late life dementing illnesses, particularly Alzheimer's disease. A "Systematic Review" from the US Agency for Healthcare Research and Quality and the National Institute on Aging concluded that because the overall quality of evidence was low, recommendations for public health could not be made. In order to gain evidence for the efficacy of lifestyle interventions, we propose a "Modest Proposal" to study 10,000 subjects over 40 years randomly assigned to groups of low or high saturated fat in the diet, head injury, and high or low levels of mental activity, physical activity, or inactivity as well as smoking or non-smoking. This proposed study cannot be accomplished. The "Modest Proposal" illustrates that the absence of definitive evidence should not restrict physicians from making reasonable recommendations based on the evidence that is available.

Association of Coffee Drinking with Total and Cause-Specific Mortality

Background Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear. Methods We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health–AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline. Results During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline. Conclusions In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.)

Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice.

Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.

Comparison of the cytotoxic and mutagenic potential of liquid smoke food flavourings, cigarette smoke condensate and wood smoke condensate.

Although products of pyrolysis are often cytotoxic and mutagenic, the relationship between the type of material pyrolysed and the toxicity of the resulting pyrolysis products is poorly understood. The objective of this study was to evaluate and compare the cytotoxicity and mutagenicity of several types of common pyrolysis products. The cytotoxicity and mutagenicity of these products were assessed by using neutral red uptake and Ames mutagenicity assays, respectively. The biological activities of four liquid smoke food flavourings (LSF) were compared with two other pyrolysis-derived materials; cigarette smoke condensate (CSC) and a wood smoke condensate (WSC). Results indicated all of the mixtures exhibited a concentration-dependent cytotoxic response. The CSC and WSC were less cytotoxic than three of the LSFs, but more cytotoxic than one of the brands. The CSC was mutagenic in two Salmonella strains; however, none of the LSFs or WSC was mutagenic using TA98, and only three of the LSFs were positive with TA100. The six pyrolysis-derived materials evaluated in this study showed differing patterns and magnitudes of cytotoxicity and mutagenicity. These results indicate that the cytotoxicity and mutagenicity of complex mixtures derived from pyrolysis products are affected by the type of material pyrolysed and/or the method used to prepare the mixture. The cytotoxic potential of some commercial smoke flavourings is greater than cigarette smoke condensate and several of the food flavourings are mutagenic in one Salmonella strain.

Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial.

Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.

Molecular mechanisms of alcohol-mediated carcinogenesis.

Approximately 3.6% of cancers worldwide derive from chronic alcohol drinking, including those of the upper aerodigestive tract, the liver, the colorectum and the breast. Although the mechanisms for alcohol-associated carcinogenesis are not completely understood, most recent research has focused on acetaldehyde, the first and most toxic ethanol metabolite, as a cancer-causing agent. Ethanol may also stimulate carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism. Alcohol-related carcinogenesis may interact with other factors such as smoking, diet and comorbidities, and depends on genetic susceptibility.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010

Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.

Cooked meat and risk of breast cancer--lifetime versus recent dietary intake.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.

Ageing and eating.

Epidemiological studies propose that extension of the human lifespan or the reduction of age associated diseases may be achieved by physical exercise, caloric restriction, and by consumption of certain substances such as resveratrol, selenium, flavonoids, zinc, omega 3 unsaturated fatty acids, vitamins E and C, Ginkgobiloba extracts, aspirin, green tea catechins, antioxidants in general, and even by light caffeine or alcohol consumption. Though intriguing, these studies only show correlative (not causative) effects between the application of the particular substance and longevity. On the other hand, obesity is yet a strong menace to the western society and it will emerge even more so throughout the next decades according to the prediction of the WHO. Although obesity is considered a severe problem, very little is known about the molecular mechanisms causing the associated degeneration of organs and finally death. Nutrient related adverse consequences for health and thus ageing may be due to a high sugar or high fat diet, excessive alcohol consumption and cigarette smoke amongst others. In this article we examine the interdependencies of eating and ageing and suggest yeast, one of the most successful ageing models, as an easy tool to elucidate the molecular pathways from eating to ageing. The conservation of most ageing pathways in yeast and their easy genetic tractability may provide a chance to discriminate between the correlative and causative effects of nutrition on ageing. 2010 Elsevier B.V. All rights reserved.

Occupational toxicology of asbestos-related malignancies.

INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.

Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study

Background There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. Methods and Findings We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1–14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass–, and social class–adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21–1.60), 1.95 (1.70–-2.25), 2.52 (2.13–3.00), and 4.04 (2.95–5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. Conclusions Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.  Editors' Summary Background. Every day, or so it seems, new research shows that some aspect of lifestyle—physical activity, diet, alcohol consumption, and so on—affects health and longevity. For the person in the street, all this information is confusing. What is a healthy diet, for example? Although there are some common themes such as the benefit of eating plenty of fruit and vegetables, the details often differ between studies. And exactly how much physical activity is needed to improve health? Is a gentle daily walk sufficient or simply a stepping stone to doing enough exercise to make a real difference? The situation with alcohol consumption is equally confusing. Small amounts of alcohol apparently improve health but large amounts are harmful. As a result, it can be hard for public-health officials to find effective ways to encourage the behavioral changes that the scientific evidence suggests might influence the health of populations. Why Was This Study Done? There is another factor that is hindering official attempts to provide healthy lifestyle advice to the public. Although there is overwhelming evidence that individual behavioral factors influence health, there is very little information about their combined impact. If the combination of several small differences in lifestyle could be shown to have a marked effect on the health of populations, it might be easier to persuade people to make behavioral changes to improve their health, particularly if those changes were simple and relatively easy to achieve. In this study, which forms part of the European Prospective Investigation into Cancer and Nutrition (EPIC), the researchers have examined the relationship between lifestyle and the risk of dying using a health behavior score based on four simply defined behaviors—smoking, physical activity, alcohol drinking, and fruit and vegetable intake. What Did the Researchers Do and Find? Between 1993 and 1997, about 20,000 men and women aged 45–79 living in Norfolk UK, none of whom had cancer or cardiovascular disease (heart or circulation problems), completed a health and lifestyle questionnaire, had a health examination, and had their blood vitamin C level measured as part of the EPIC-Norfolk study. A health behavior score of between 0 and 4 was calculated for each participant by giving one point for each of the following healthy behaviors: current non-smoking, not physically inactive (physical inactivity was defined as having a sedentary job and doing no recreational exercise), moderate alcohol intake (1–14 units a week; a unit of alcohol is half a pint of beer, a glass of wine, or a shot of spirit), and a blood vitamin C level consistent with a fruit and vegetable intake of at least five servings a day. Deaths among the participants were then recorded until 2006. After allowing for other factors that might have affected their likelihood of dying (for example, age), people with a health behavior score of 0 were four times as likely to have died (in particular, from cardiovascular disease) than those with a score of 4. People with a score of 2 were twice as likely to have died. What Do These Findings Mean? These findings indicate that the combination of four simply defined health behaviors predicts a 4-fold difference in the risk of dying over an average period of 11 years for middle-aged and older people. They also show that the risk of death (particularly from cardiovascular disease) decreases as the number of positive health behaviors increase. Finally, they can be used to calculate that a person with a health score of 0 has the same risk of dying as a person with a health score of 4 who is 14 years older. These findings need to be confirmed in other populations and extended to an analysis of how these combined health behaviors affect the quality of life as well as the risk of death. Nevertheless, they strongly suggest that modest and achievable lifestyle changes could have a marked effect on the health of populations. Armed with this information, public-health officials should now be in a better position to encourage behavior changes likely to improve the health of middle-aged and older people. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050012.

Concentrations of polybrominated diphenyl ethers, hexachlorobenzene and polycyclic aromatic hydrocarbons in various foodstuffs before and after coo...

The cooking-induced changes in the levels of polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), and 16 polycyclic aromatic hydrocarbons (PAHs) in various foodstuffs were investigated. Foods included fish (sardine, hake and tuna), meat (veal steak, loin of pork, breast and thigh of chicken, and steak and rib of lamb), string bean, potato, rice, and olive oil. For each food item, raw and cooked (fried, grilled, roasted, boiled) samples were analyzed. There were some variations in the concentrations of PBDEs before and after cooking. However, they depended not only on the cooking process, but mainly on the specific food item. The highest HCB concentrations were found in sardine, being lower in cooked samples. All cooking processes enhanced HCB levels in hake, while very scarce differences could be noted in tuna (raw and cooked). In general terms, the highest PAH concentrations were found after frying by being the values especially notable in fish, excepting hake, where the highest total PAH levels corresponded to roasted samples. The results of this study show that, in general, cooking processes are only of a limited value as a means of reducing PBDE, HCB and PAH concentrations in food.

Review of epidemiologic studies of dietary acrylamide intake and the risk of cancer.

Conjectured associations between dietary acrylamide intake and cancer have been evaluated in more than 15 epidemiologic studies examining almost every major cancer site. We have critically reviewed the epidemiologic studies of estimated dietary acrylamide exposure and cancer. As substantially greater acrylamide exposure occurs through tobacco smoke than dietary exposure, we present the results separately for never smokers or adjusted statistically for smoking status, where possible. After an extensive examination of the published literature, we found no consistent or credible evidence that dietary acrylamide increases the risk of any type of cancer in humans, either overall or among nonsmokers. In particular, the collective evidence suggests that a high level of dietary acrylamide intake is not a risk factor for breast, endometrial, or ovarian cancers, which have generated particular interest because of a conjectured hormonal mechanism of acrylamide. Moreover, the absence of a positive association between smoking and ovarian and endometrial cancers suggests that any association of these cancers with the much lower, more sporadic dietary acrylamide intake is unlikely. In conclusion, epidemiologic studies of dietary acrylamide intake have failed to demonstrate an increased risk of cancer. In fact, the sporadically and slightly increased and decreased risk ratios reported in more than two dozen papers examined in this review strongly suggest the pattern one would expect to find for a true null association over the course of a series of trials. Therefore, continued epidemiologic investigation of acrylamide and cancer risk appears to be a misguided research priority.

Cooking frequency may enhance survival in Taiwanese elderly.

OBJECTIVE: To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese. DESIGN: Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments. SETTING: Elderly Nutrition and Health Survey in Taiwan, 1999-2000. SUBJECTS: Nationally representative free-living elderly people aged ≥65 years (n 1888). RESULTS: During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings. CONCLUSIONS: Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.

Polybrominated diphenyl ethers in food and human dietary exposure: a review of the recent scientific literature.

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) used to protect people from fires by reducing the flammability of combustible materials. In recent years, PBDEs have become widespread environmental pollutants, while body burden in the general population has been increasing. A number of studies have shown that, as for other persistent organic pollutants, dietary intake is one of the main routes of human exposure to PBDEs. The most recent scientific literature concerning the levels of PBDEs in foodstuffs and the human dietary exposure to these BFRs are here reviewed. It has been noted that the available information on human total daily intake through food consumption is basically limited to a number of European countries, USA, China, and Japan. In spite of the considerable methodological differences among studies, the results show notable coincidences such as the important contribution to the sum of total PBDEs of some congeners such as BDEs 47, 49, 99 and 209, the comparatively high contribution of fish and seafood, and dairy products, and the probably limited human health risks derived from dietary exposure to PBDEs. Various issues directly related to human exposure to PBDEs through the diet still need investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Determination of total N-nitroso compounds and their precursors in frankfurters, fresh meat, dried salted fish, sauces, tobacco, and tobacco smoke ...

Total N-nitroso compounds (NOC) and NOC precursors (NOCP) were determined in extracts of food and tobacco products. Following Walters' method, NOC were decomposed to NO with refluxing HBr/HCl/HOAc/EtOAc and NO was measured by chemiluminescence. NOC were determined after sulfamic acid treatment to destroy nitrite, and NOCP were determined after treatment with 110 mM nitrite and then sulfamic acid. Analysis without HBr gave results < or =20% of those with HBr. This NOC method was efficient for nitrosamines but not nitrosoureas. The standard nitrosation for determining NOCP gave high yields for readily nitrosated amines, including 1-deoxy-1-fructosylvaline, but not for simple amines, dipeptides, and alkylureas. Mean NOC and NOCP results were (respectively, in micromol/kg of product) 5.5 and 2700 for frankfurters, 0.5 and 660 for fresh meat, 5.8 and 5800 for salted, dried fish, and 660 and 2900 for chewing tobacco (all for aqueous extracts) and 220 and 20000 nmol/cigarette for MeCN extracts of cigarette smoke filter pads.

Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.

The link between erectile and cardiovascular health: the canary in the coal mine.

Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.

Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure.

High-level cadmium (Cd) exposure has long been known to induce nephropathy, severe osteoporosis, and fractures in humans. More recent epidemiology, however, reveals that, in populations not known to have important industrial exposure to this heavy metal, high-normal blood or urine Cd levels correlate with increased risk for vascular disorders, cancers, diabetes, and total mortality, as well as osteoporosis and nephropathy. Since these disorders appear unlikely to expedite Cd absorption, and since Cd has promoted these pathologies in rodent studies, it seems reasonable to conclude that Cd is an important mediating risk factor for these disorders in humans. Avoiding tobacco smoke or frequent ingestion of shellfish or organ meats can lessen humans exposure to Cd, but the chief dietary sources of Cd are plant-derived foods - green leafy vegetables, whole grains, tubers, and root vegetables - typically recommended for their health-supportive properties; indeed, among non-smokers, vegans tend to have the highest Cd body burden. Fortunately, iron sufficiency and ample dietary intakes of calcium, magnesium, and zinc can impede absorption of dietary Cd, both by down-regulating intestinal expression of mineral transporters, and by directly competing with Cd for access to these transporters. Correction of iron deficiency appears to be of particular importance for controlling Cd absorption. Moreover, zinc supplementation can counteract the toxicity of Cd already in the body via induction of metallothionein, which binds Cd avidly via its sulfhydryl groups; so long as it remains sequestered in this form, Cd is innocuous. Zinc supplementation may in any case be recommendable, as optimal zinc status exerts protective anti-inflammatory, antioxidant, and immunosupportive effects. Inasmuch as the toxicity of Cd appears to be mediated in large part by oxidative stress, ingestion of spirulina, lipoic acid, melatonin, and N-acetylcysteine may also have potential for mitigating the risk associated with Cd exposure, as suggested by rodent studies. Hence, although Cd may prove to be a major risk factor for morbidity and mortality in humans, practical strategies for limiting its absorption and pathogenic impact are at hand. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multivitamin Use and the Risk of Mortality and Cancer Incidence

Although multivitamin/mineral supplements are commonly used in the United States, the efficacy of these supplements in preventing chronic disease or premature death is unclear. To assess the relation of multivitamin use with mortality and cancer, the authors prospectively examined these associations among 182,099 participants enrolled in the Multiethnic Cohort Study between 1993 and 1996 in Hawaii and California. During an average 11 years of follow-up, 28,851 deaths were identified. In Cox proportional hazards models controlling for tobacco use and other potential confounders, no associations were found between multivitamin use and mortality from all causes (for users vs. nonusers: hazard ratio = 1.07, 95% confidence interval: 0.96, 1.19 for men; hazard ratio = 0.96, 95% confidence interval: 0.85, 1.09 for women), cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status. There also was no evidence indicating that multivitamin use was associated with risk of cancer, overall or at major sites, such as lung, colorectum, prostate, and breast. In conclusion, there was no clear decrease or increase in mortality from all causes, cardiovascular disease, or cancer and in morbidity from overall or major cancers among multivitamin supplement users.

Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.

An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.

Low-Risk Lifestyle Behaviors and All-Cause Mortality: Findings From the National Health and Nutrition Examination Survey III Mortality Study

Objectives. We examined the relationship between 4 low-risk behaviors—never smoked, healthy diet, adequate physical activity, and moderate alcohol consumption—and mortality in a representative sample of people in the United States. Methods. We used data from 16958 participants aged 17 years and older in the National Health and Nutrition Examination Survey III Mortality Study from 1988 to 2006. Results. The number of low-risk behaviors was inversely related to the risk for mortality. Compared with participants who had no low-risk behaviors, those who had all 4 experienced reduced all-cause mortality (adjusted hazard ratio [AHR]=0.37; 95% confidence interval [CI]=0.28, 0.49), mortality from malignant neoplasms (AHR=0.34; 95% CI=0.20, 0.56), major cardiovascular disease (AHR=0.35; 95% CI=0.24, 0.50), and other causes (AHR=0.43; 95% CI=0.25, 0.74). The rate advancement periods, representing the equivalent risk from a certain number of years of chronological age, for participants who had all 4 high-risk behaviors compared with those who had none were 11.1 years for all-cause mortality, 14.4 years for malignant neoplasms, 9.9 years for major cardiovascular disease, and 10.6 years for other causes. Conclusions. Low-risk lifestyle factors exert a powerful and beneficial effect on mortality.

Effects of a high-fat meal on pulmonary function in healthy subjects.

Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.

The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors

Background Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for Editors' Summary Editors' Summary A number of modifiable factors are responsible for many premature or preventable deaths. For example, being overweight or obese shortens life expectancy, while half of all long-term tobacco smokers in Western populations will die prematurely from a disease directly related to smoking. Modifiable risk factors fall into three main groups. First, there are lifestyle risk factors. These include tobacco smoking, physical inactivity, and excessive alcohol use (small amounts of alcohol may actually prevent diabetes and some types of heart disease and stroke). Second, there are dietary risk factors such as a high salt intake and a low intake of fruits and vegetables. Finally, there are “metabolic risk factors,” which shorten life expectancy by increasing a person's chances of developing cardiovascular disease (in particular, heart problems and strokes) and diabetes. Metabolic risk factors include having high blood pressure or blood cholesterol and being overweight or obese. Why Was This Study Done? It should be possible to reduce preventable deaths by changing modifiable risk factors through introducing public health policies, programs and regulations that reduce exposures to these risk factors. However, it is important to know how many deaths are caused by each risk factor before developing policies and programs that aim to improve a nation's health. Although previous studies have provided some information on the numbers of premature deaths caused by modifiable risk factors, there are two problems with these studies. First, they have not used consistent and comparable methods to estimate the number of deaths attributable to different risk factors. Second, they have rarely considered the effects of dietary and metabolic risk factors. In this new study, the researchers estimate the number of deaths due to 12 different modifiable dietary, lifestyle, and metabolic risk factors for the United States population. They use a method called “comparative risk assessment.” This approach estimates the number of deaths that would be prevented if current distributions of risk factor exposures were changed to hypothetical optimal distributions. What Did the Researchers Do and Find? The researchers extracted data on exposures to these 12 selected risk factors from US national health surveys, and they obtained information on deaths from difference diseases for 2005 from the US National Center for Health Statistics. They used previously published studies to estimate how much each risk factor increases the risk of death from each disease. The researchers then used a mathematical formula to estimate the numbers of deaths caused by each risk factor. Of the 2.5 million US deaths in 2005, they estimate that nearly half a million were associated with tobacco smoking and about 400,000 were associated with high blood pressure. These two risk factors therefore each accounted for about 1 in 5 deaths in US adults. Overweight–obesity and physical inactivity were each responsible for nearly 1 in 10 deaths. Among the dietary factors examined, high dietary salt intake had the largest effect, being responsible for 4% of deaths in adults. Finally, while alcohol use prevented 26,000 deaths from ischemic heart disease, ischemic stroke, and diabetes, the researchers estimate that it caused 90,000 deaths from other types of cardiovascular diseases, other medical conditions, and road traffic accidents and violence. What Do These Findings Mean? These findings indicate that smoking and high blood pressure are responsible for the largest number of preventable deaths in the US, but that several other modifiable risk factors also cause many deaths. Although the accuracy of some of the estimates obtained in this study will be affected by the quality of the data used, these findings suggest that targeting a handful of risk factors could greatly reduce premature mortality in the US. The findings might also apply to other countries, although the risk factors responsible for most preventable deaths may vary between countries. Importantly, effective individual-level and population-wide interventions are already available to reduce people's exposure to the two risk factors responsible for most preventable deaths in the US. The researchers also suggest that combinations of regulation, pricing, and education have the potential to reduce the exposure of US residents to other risk factors that are likely to shorten their lives. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000058.

Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.

The counseling practices of internists.

OBJECTIVES: To determine the counseling practices of a group of internists in the areas of smoking, exercise, and alcohol and seat belt use, and to determine the associations among physicians' personal health habits and their counseling practices. DESIGN: A random stratified sample of members and fellows of the American College of Physicians in 21 regions selected to represent all areas of the United States. Because of the relatively small proportion of women in this group, they were oversampled. SETTING: Physicians' practices. PARTICIPANTS: One thousand three hundred and forty-nine internists (members or fellows of the College) returned questionnaires, for a response rate of 75%; 52% defined themselves as general internists. INTERVENTIONS: A questionnaire was used to obtain information on internists' use of cigarettes, alcohol, and seat belts and their level of physical activity. Data were obtained on the indications used for counseling and the aggressiveness of counseling about each of these four habits. MEASUREMENTS AND MAIN RESULTS: Bivariate and logistic regression analyses were used to compare the tendencies of internist subgroups both in using various indications for counseling and in the thoroughness of counseling. Generalists were more likely than specialists to counsel at least once all patients who were at risk and to be more aggressive in counseling. Ninety percent of respondents counseled all of their patients who smoked, but 64.5% never discussed the use of seat belts. Only 3.8% of these internists currently smoked cigarettes, 11.3% drank alcohol daily, 38.7% were extremely or quite active, and 87.3% used seat belts all or most of the time. Among men internists, for every habit except alcohol use, personal health practices were substantially associated with counseling patients; for example, nonsmoking internists were more likely to counsel smokers, and very physically active internists were more likely to counsel about exercise. Among women internists, being very physically active was associated with counseling more patients about exercise and alcohol use. CONCLUSIONS: The low level of self-reported counseling among these internists suggests that further emphasis on training in these skills is needed. The association between personal and professional practices suggests that medical schools and housestaff training programs should support health promotion activities for future internists.

Cancer is a Preventable Disease that Requires Major Lifestyle Changes

This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes.

Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer

Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer.

Towards a new system of health: the challenge of Western disease.

Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease ("complex research") to studying the role of lifestyle factors ("simple research").

Temporal and Regional Trends in the Prevalence of Healthy Lifestyle Characteristics: United States, 1994–2007

Objectives. We examined temporal and regional trends in the prevalence of health lifestyles in the United States. Methods. We used 1994 to 2007 data from the Behavioral Risk Factor Surveillance System to assess 4 healthy lifestyle characteristics: having a healthy weight, not smoking, consuming fruits and vegetables, and engaging in physical activity. The concurrent presence of all 4 characteristics was defined as a healthy overall lifestyle. We used logistic regression to assess temporal and regional trends. Results. The percentages of individuals who did not smoke (4% increase) and had a healthy weight (10% decrease) showed the strongest temporal changes from 1994 to 2007. There was little change in fruit and vegetable consumption or physical activity. The prevalence of healthy lifestyles increased minimally over time and varied modestly across regions; in 2007, percentages were higher in the Northeast (6%) and West (6%) than in the South (4%) and Midwest (4%). Conclusions. Because of the large increases in overweight and the declines in smoking, there was little net change in the prevalence of healthy lifestyles. Despite regional differences, the prevalence of healthy lifestyles across the United States remains very low.

Manufactured uncertainty: protecting public health in the age of contested science and product defense.

The strategy of "manufacturing uncertainty" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called "product defense" or "litigation support." As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.

Environmental contaminants as risk factors for developing diabetes.

The contribution of exposure to persistent organic pollutants (POPs) to the incidence of diabetes has received little attention until recently. A number of reports have emerged, however, concerning elevated diabetes in persons occupationally exposed to dioxin. United States (US) Air Force personnel in Vietnam who sprayed Agent Orange containing dioxin as a contaminant had elevated rates of diabetes, leading to US government compensation for diabetes in these veterans. Recent studies in populations exposed to polychlorinated biphenyls (PCBs) and chlorinated pesticides found a dose-dependent elevated risk of diabetes. An elevation in risk of diabetes in relation to levels of several POPs has been demonstrated by two different groups using the National Health and Nutrition Examination Survey (NHANES), a random sampling of US citizens. The strong associations seen in quite different studies suggest the possibility that exposure to POPs could cause diabetes. One striking observation is that obese persons that do not have elevated POPs are not at elevated risk of diabetes, suggesting that the POPs rather than the obesity per se is responsible for the association. Although a specific mechanism is not known, most POPs induce a great number and variety of genes, including several that alter insulin action. Because diabetes is a dangerous disease that is increasing in frequency throughout the world, further study of the possibility that exposure to POPs contributes to the etiology of diabetes is critical.

Lung deposition of fine and ultrafine particles outdoors and indoors during a cooking event and a no activity period.

Some indoor activities increase the number concentration of small particles and, hence, enhance the dose delivered to the lungs. The received particle dose indoors may exceed noticeably the dose from ambient air under routine in-house activities like cooking. In the present work, the internal dose by inhalation of ultrafine and fine particles is assessed, using an appropriate mechanistic model of lung deposition, accommodating aerosol, and inhalation dynamics. The analysis is based on size distribution measurements (10-350 nm) of indoor and outdoor aerosol number concentrations in a typical residence in Athens, Greece. Four different cases are examined, namely, a cooking event, a no activity period indoors and the equivalent time periods outdoors. When the cooking event (frying of bacon-eggs with a gas fire) occurred, the amount of deposited particles deep into the lung of an individual indoors exceeded by up to 10 times the amount received by an individual at the same time period outdoors. The fine particle deposition depends on the level of physical exertion and the hygroscopic properties of the inhaled aerosol. The dose is not found linearly dependant on the indoor/outdoor concentrations during the cooking event, whereas it is during the no activity period. PRACTICAL IMPLICATIONS: The necessity for determining the dose in specific regions of the human lung, as well as the non-linear relationship between aerosol concentration and internal dose makes the application of dosimetry models important. Lung dose of fine and ultrafine particles, during a cooking event, is compared with the dose at no indoor activity and the dose received under outdoor exposure conditions. The dose is expressed in terms of number or surface of deposited particles. This permits to address the dosimetry of very small particles, which are released by many indoor sources but represent a slight fraction of the particulate matter mass. The enhancement of the internal dose resulting from fine and ultrafine particles generated during the cooking event vs. the dose when no indoor source is active is assessed. The results for those cases are also compared with the dose calculated for the measured aerosol outdoors.

The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases.

This review reconsiders a major cause of cardiovascular diseases, tobacco smoking, as the activation of the Aryl hydrocarbon Receptor (AhR), also known as the dioxin receptor, by aryl hydrocarbons from the tar fraction of tobacco in various organs of the cardiovascular domain. This concept sheds new light on well-known albeit controversial epidemiological concepts such as the Mediterranean diet and the French paradox. We also review the discovery that resveratrol, a natural AhR antagonist, may be of interest in the prevention and treatment of cardiovascular diseases.

Egg consumption and the risk of cancer: a multisite case-control study in Uruguay.

BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.

Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women.

BACKGROUND: Limited data are available on the benefit of combining healthy dietary and lifestyle behaviors in the prevention of myocardial infarction (MI) in women. METHODS: We used factor analysis to identify a low-risk behavior-based dietary pattern in 24 444 postmenopausal women from the population-based prospective Swedish Mammography Cohort who were free of diagnosed cancer, cardiovascular disease, and diabetes mellitus at baseline (September 15, 1997). We also defined 3 low-risk lifestyle factors: nonsmoking, waist-hip ratio less than the 75th percentile (< 0.85), and being physically active (at least 40 minutes of daily walking or bicycling and 1 hour of weekly exercise). RESULTS: During 6.2 years (151 434 person-years) of follow-up, we ascertained 308 cases of primary MI. Two major identified dietary patterns, "healthy" and "alcohol," were significantly associated with decreased risk of MI. The low-risk diet (high scores for the healthy dietary pattern) characterized by a high intake of vegetables, fruit, whole grains, fish, and legumes, in combination with moderate alcohol consumption (>/= 5 g of alcohol per day), along with the 3 low-risk lifestyle behaviors, was associated with 92% decreased risk (95% confidence interval, 72%-98%) compared with findings in women without any low-risk diet and lifestyle factors. This combination of healthy behaviors, present in 5%, may prevent 77% of MIs in the study population. CONCLUSION: Most MIs in women may be preventable by consuming a healthy diet and moderate amounts of alcohol, being physically active, not smoking, and maintaining a healthy weight.

A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer.

BACKGROUND: Acrylamide, a probable human carcinogen, was detected in various heat-treated carbohydrate-rich foods in 2002. The few epidemiologic studies done thus far have not shown a relationship with cancer. Our aim was to investigate the association between acrylamide intake and endometrial, ovarian, and breast cancer risk. METHODS: The Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline (1986), a random subcohort of 2,589 women was selected using a case cohort analysis approach for analysis. The acrylamide intake of subcohort members and cases was assessed with a food frequency questionnaire and was based on chemical analysis of all relevant Dutch foods. Subgroup analyses were done for never-smokers to eliminate the influence of smoking; an important source of acrylamide. RESULTS: After 11.3 years of follow-up, 327, 300, and 1,835 cases of endometrial, ovarian, and breast cancer, respectively, were documented. Compared with the lowest quintile of acrylamide intake (mean intake, 8.9 mug/day), multivariable-adjusted hazard rate ratios (HR) for endometrial, ovarian, and breast cancer in the highest quintile (mean intake, 40.2 mug/day) were 1.29 [95% confidence interval (95% CI), 0.81-2.07; P(trend)=0.18], 1.78 (95% CI, 1.10-2.88; P(trend)=0.02), and 0.93 (95% CI, 0.73-1.19; P(trend)=0.79), respectively. For never-smokers, the corresponding HRs were 1.99 (95% CI, 1.12-3.52; P(trend)=0.03), 2.22 (95% CI, 1.20-4.08; P(trend)=0.01), and 1.10 (95% CI, 0.80-1.52; P(trend)=0.55). CONCLUSIONS: We observed increased risks of postmenopausal endometrial and ovarian cancer with increasing dietary acrylamide intake, particularly among never-smokers. Risk of breast cancer was not associated with acrylamide intake.

They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals.

OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.

Healthy living is the best revenge: findings from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study.

BACKGROUND: Our objective was to describe the reduction in relative risk of developing major chronic diseases such as cardiovascular disease, diabetes, and cancer associated with 4 healthy lifestyle factors among German adults. METHODS: We used data from 23,153 German participants aged 35 to 65 years from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. End points included confirmed incident type 2 diabetes mellitus, myocardial infarction, stroke, and cancer. The 4 factors were never smoking, having a body mass index lower than 30 (calculated as weight in kilograms divided by height in meters squared), performing 3.5 h/wk or more of physical activity, and adhering to healthy dietary principles (high intake of fruits, vegetables, and whole-grain bread and low meat consumption). The 4 factors (healthy, 1 point; unhealthy, 0 points) were summed to form an index that ranged from 0 to 4. RESULTS: During a mean follow-up of 7.8 years, 2006 participants developed new-onset diabetes (3.7%), myocardial infarction (0.9%), stroke (0.8%), or cancer (3.8%). Fewer than 4% of participants had zero healthy factors, most had 1 to 3 healthy factors, and approximately 9% had 4 factors. After adjusting for age, sex, educational status, and occupational status, the hazard ratio for developing a chronic disease decreased progressively as the number of healthy factors increased. Participants with all 4 factors at baseline had a 78% (95% confidence interval [CI], 72% to 83%) lower risk of developing a chronic disease (diabetes, 93% [95% CI, 88% to 95%]; myocardial infarction, 81% [95% CI, 47% to 93%]; stroke, 50% [95% CI, -18% to 79%]; and cancer, 36% [95% CI, 5% to 57%]) than participants without a healthy factor. CONCLUSION: Adhering to 4 simple healthy lifestyle factors can have a strong impact on the prevention of chronic diseases.

Cancer incidence among Danish Seventh-day Adventists and Baptists.

INTRODUCTION: American Seventh-day Adventists have been reported to have lower cancer mortality and incidence than the general population. Adventists do not consume tobacco, alcohol or pork, and many adhere to a lacto-ovo-vegetarian lifestyle. Baptists discourage excessive use of alcohol and tobacco. In this study, we investigated whether the incidence of cancer in a large cohort of Danish Adventists and Baptists was different compared to the general Danish population. MATERIAL AND METHODS: We followed 11,580 Danish Adventists and Baptists in the nationwide Danish Cancer Registry, which contains information on cases of cancer for 1943-2008. Cancer incidence in the cohort was compared with that in the general Danish population as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), and within-cohort comparisons were made with a Cox model. RESULTS: Lower cancer incidences were observed for both Seventh-day Adventist men (SIR, 66; 95% CI, 60-72) and women (85; 80-91). The same result was observed for Baptists although not as low. The differences were most pronounced for smoking-related cancers such as those of the buccal cavity and lung (SIR, 20; 13-30 for Seventh-day Adventist men and 33; 22-49 for Seventh-day Adventist women). The incidences of other lifestyle-related cancers, such as of stomach, rectum, liver and cervix, were also decreased. In general, the SIRs were lower for men than for women, and Adventists had lower hazard rates than Baptists. DISCUSSION: Our findings point to the benefits of compliance with public health recommendations and indicate that lifestyle changes in the population might change the cancer risks of individuals. Copyright © 2012 Elsevier Ltd. All rights reserved.

The opioid system and food intake: homeostatic and hedonic mechanisms.

Opioids are important in reward processes leading to addictive behavior such as self-administration of opioids and other drugs of abuse including nicotine and alcohol. Opioids are also involved in a broadly distributed neural network that regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In this sense, opioids are particularly implicated in the modulation of highly palatable foods, and opioid antagonists attenuate both addictive drug taking and appetite for palatable food. Thus, craving for palatable food could be considered as a form of opioid-related addiction. There are three main families of opioid receptors (µ, ĸ, and δ) of which µ-receptors are most strongly implicated in reward. Administration of selective µ-agonists into the NAcc of rodents induces feeding even in satiated animals, while administration of µ-antagonists reduces food intake. Pharmacological studies also suggest a role for ĸ- and δ-opioid receptors. Preliminary data from transgenic knockout models suggest that mice lacking some of these receptors are resistant to high-fat diet-induced obesity. Copyright © 2012 S. Karger GmbH, Freiburg.

No Association of Coffee Consumption with Gastric Ulcer, Duodenal Ulcer, Reflux Esophagitis, and Non-Erosive Reflux Disease: A Cross-Sectional Study of 8,013 Healthy Subjects in Japan

Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.

Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man.

The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.

Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring

Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.

Healthy lifestyle on the risk of breast cancer.

BACKGROUND: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer. METHODS: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association. RESULTS: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared. CONCLUSIONS: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. IMPACT: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. ©2011 AACR.

MPTP: an industrial chemical and contaminant of illicit narcotics stimulates a new era in research on Parkinson's disease.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes selective destruction of dopaminergic neurons of the nigrostriatal pathway in humans and other primates. It is less specific and much less potent in mice and has only slight effects in rats. Differences in rates and sites of metabolism of MPTP to its active, toxic, highly polar metabolite, MPP+ (1-methyl-4-phenylpyridine), appear to influence species specificity. In rats, type B monoamine oxidase (MAO-B), which mediates the conversion of MPTP to MPP+, may act as an enzymatic barrier at brain microvessels, whereas in primates the enzyme, present mainly in astrocytes, appears important for bioactivation of MPTP into the toxic metabolite. MPP+ is a substrate for catecholamine uptake sites and is concentrated in these neurons. The molecular mechanism of MPP+ toxicity has not been established definitively, but conversion to a free radical or uptake by mitochondria and inhibition of mitochondrial respiratory enzymes, leading to calcium release and cell death have been suggested. The discovery of toxin which causes an animal model of Parkinson's disease has stimulated new research on environmental factors that might contribute to this progressive degenerative disorder and provides a means for assessing new approaches to therapy.

Risk factors for myocardial infarction in women and men: insights from the INTERHEART study.

AIMS: Coronary heart disease (CHD) is a leading cause of death among men and women globally. Women develop CHD about 10 years later than men, yet the reasons for this are unclear. The purpose of this report is to determine if differences in risk factor distributions exist between women and men across various age categories to help explain why women develop acute MI later than men. METHODS AND RESULTS: We used the INTERHEART global case-control study including 27 098 participants from 52 countries, 6787 of whom were women. The median age of first acute MI was higher in women than men (65 vs. 56 years; P < 0.0001). Nine modifiable risk factors were associated with MI in women and men. Hypertension [2.95(2.66 -3.28) vs. 2.32(2.16-2.48)], diabetes [4.26(3.68-4.94) vs. 2.67(2.43-2.94), physical activity [0.48(0.41-0.57) vs. 0.77(0.71-0.83)], and moderate alcohol use [0.41(0.34-0.50) vs. 0.88(0.82-0.94)] were more strongly associated with MI among women than men. The association of abnormal lipids, current smoking, abdominal obesity, high risk diet, and psychosocial stress factors with MI was similar in women and men. Risk factors associations were generally stronger among younger individuals compared to older women and men. The population attributable risk (PAR) of all nine risk factors exceeded 94%, and was similar among women and men (96 vs. 93%). Men were significantly more likely to suffer a MI prior to 60 years of age than were women, however, after adjusting for levels of risk factors, the sex difference in the probability of MI cases occurring before the age of 60 years was reduced by more than 80%. CONCLUSION: Women experience their first acute MI on average 9 years later than men. Nine modifiable risk factors are significantly associated with acute MI in both men and women and explain greater than 90% of the PAR. The difference in age of first MI is largely explained by the higher risk factor levels at younger ages in men compared to women.

N-Nitroso compounds in the diet.

N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.

Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund.

BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.

Short- and long-term morbidity and mortality in the population exposed to dioxin after the "Seveso accident".

The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.

A Multicountry Ecological Study of Cancer Incidence Rates in 2008 with Respect to Various Risk-Modifying Factors

Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.

Effect of spiced food on metabolic rate.

Since the time of Lavoisier it has been known that the ingestion of food in animals and man produces an increase in oxygen consumption. This increase in metabolic rate was originally called 'specific dynamic action' (SDA) and is now widely referred to as the thermic effect (TE) of food or diet-induced thermogenesis (DIT) (Rothwell & Stock, 1981). Much of the early work on the thermic effect was confined to the type and amount of food, notably the macronutrients--proteins, fats and carbohydrates. Later, it was shown that certain minor constituents of the diet such as caffeine and associated methylxanthines (Zahorska-Markrewicz, 1980; Jung et al., 1981) in tea and coffee could also have a profound effect on metabolic rate. The consumption of alcohol was also shown to increase metabolic rate (Rosenberg & Durnin, 1978). The work described in this paper reports the effect of another minor constituent of food, spices, on metabolic rate. Although the use of spices in our food has steadily increased with time little information exists on their effect on the metabolic rate. It has been estimated that approximately 40 different spices are used in our diet today. This communication reports the effect of chilli (red pepper, capsicum annuum) and mustard (Brassica juncea).

Nutritional risk factors for the development of chronic obstructive pulmonary disease (COPD) in male smokers.

BACKGROUND & AIMS: The aim of this study was to investigate whether nutritional risk factors, especially black tea consumptions, are inversely associated with the development of chronic obstructive pulmonary disease (COPD) in male smokers. METHODS: Forty male smokers with clinical diagnosis of COPD (Group-I (GI)) and 36 healthy smokers without COPD (Group-II (GII)) were included in this study. We compared the dietary habits and food intakes of the two groups using an adaptation of the Arizona Food Frequency Questionnaire (AFFQ). Question form included a list of 65 food items formed from five main food groups (grain, meat and alternatives, dairy products, vegetables-fruits and fat) and 25 dietary habits. The data were evaluated by binary logistic regression analysis, receiver operating characteristic (ROC) curve, Kolmogorov-Smirnov, Student's t, Mann-Whitney, and Chi-square tests. RESULTS: When both groups compared, black tea consumptions (GI-700ml; GII-1600ml (OR: 0.635, P<0.001)), vegetable fruits scores (GI-54.30; GII-63.81 (OR: 0.863, P<0.001)), regularly breakfast habit (GI-24 patients; GII-36 cases (OR: 0.549, P<0.001)) and eating salty (GI-22 patients; GII-5 cases (P<0.001)) made significant differences. In ROC curves, the area under the curve of black tea (0.898 (95% CI: 0.819-0.977) and vegetables-fruits (0.833 (95% CI: 0.727-0.938) provided high accuracy to distinguish between COPD group and controls (P<0.001). CONCLUSIONS: High intakes of black tea and vegetables-fruits consumptions may be protecting male smokers from developing COPD.

Adherence to healthy lifestyle habits in US adults, 1988-2006.

BACKGROUND: Lifestyle choices are associated with cardiovascular disease and mortality. The purpose of this study was to compare adherence to healthy lifestyle habits in adults between 1988 and 2006. METHODS: Analysis of adherence to 5 healthy lifestyle trends (>or=5 fruits and vegetables/day, regular exercise >12 times/month, maintaining healthy weight [body mass index 18.5-29.9 kg/m(2)], moderate alcohol consumption [up to 1 drink/day for women, 2/day for men] and not smoking) in the National Health and Nutrition Examination Survey 1988-1994 were compared with results from the National Health and Nutrition Examination Survey 2001-2006 among adults aged 40-74 years. RESULTS: Over the last 18 years, the percent of adults aged 40-74 years with a body mass index >or=30 kg/m(2) has increased from 28% to 36% (P <.05); physical activity 12 times a month or more has decreased from 53% to 43% (P <.05); smoking rates have not changed (26.9% to 26.1%); eating 5 or more fruits and vegetables a day has decreased from 42% to 26% (P <.05), and moderate alcohol use has increased from 40% to 51% (P <.05). Adherence to all 5 healthy habits has gone from 15% to 8% (P <.05). Although adherence to a healthy lifestyle was lower among minorities, adherence decreased more among non-Hispanic Whites over the period. Individuals with a history of hypertension/diabetes/cardiovascular disease were no more likely to be adherent to a healthy lifestyle than people without these conditions. CONCLUSIONS: Generally, adherence to a healthy lifestyle pattern has decreased during the last 18 years, with decreases documented in 3 of 5 healthy lifestyle habits. These findings have broad implications for the future risk of cardiovascular disease in adults.

Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.

BACKGROUND: Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. METHODS: We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15152 cases and 14820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. FINDINGS: Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. INTERPRETATION: Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction.

Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants.

OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.

Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.