***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Dietary epidemiology has been highly successful in identifying the responsible agent in many diseases , including scurvy , pellagra , blindness , and spinal bifida . Case-control , cohort , and ecologic observational studies have consistently associated increased consumption of fruits and vegetables with a decreased risk for a wide variety of epithelial cancers and , in many cases , specific dietary components seem to decrease the risk for a wide array of epithelial cancers . Over time , there has been enthusiasm for one or another compounds , such as β-carotene in the past and folate currently . Despite the success of translating similar epidemiologic observations to clinical benefit in other areas of medicine via the crucible of the r and omized clinical trial , this strategy has not been nearly as successful for cancer . We propose that the inability of nutritional epidemiology to identify effective chemopreventive strategies is not just a problem of quantitation , but rather that the discipline is usually qualitatively incapable of identifying a dietary compound(s ) that will be efficacious . One needs to consider the following basic questions in trying to underst and why nutritional epidemiology has not been translated into progress in cancer prevention : Why do fruits and vegetable show a consistent protective effect against many epithelial cancers in epidemiologic studies ? Once a specific dietary compound is identified as protective in observational studies , why do most subsequent observational studies confirm the effect ? Why are dietary epidemiology observations frequently not confirmed by the r and omized clinical trial ? We call the identified problems “ fishing with only one bait ” and the “ four-legged stool problem . ” The considerations identified in this analysis offer a number of possible solutions to puzzling findings : ( a ) Fruits and vegetables consistently show a protective effect against cancer in observational studies because they represent the entire “ biological action package . ” ( b ) Dietary compounds show a protective effect in observational studies , but not in clinical trials , because this is an inevitable consequence of one compound being falsely identified as the active agent in a system in which multiple agents or multiple interacting regulatory molecules underlie the biological effect . The consequences are serious for trying to use epidemiology to identify effective nutritional compounds . The major conclusion has to be as follows : Supplementation with single dietary compounds is rarely going to be as effective as epidemiologic studies suggest ; it is the biological action package that determines efficacy . Options for how we should move forward will be discussed . Dietary observational epidemiology is complex and involves many biases and confounders . We need to be more critical in the design of large r and omized trials based on observational epidemiology or analysis . Rules of evidence are frequently ignored or misunderstood although the limitations of observational epidemiology are analogous to the problems associated with discovery-based research and biomarker identification . We need to be much more self-critical in the important and critical assessment of dietary compounds and their role in cancer prevention given the very high appeal for this approach both within the lay and scientific communities The purpose of this study was to evaluate the effect of selenium ( Se ) in the prevention of  human primary liver cancer .  Three intervention trials were conducted among the residents at high risk to primary liver cancer ( PLC ) in Qidong county , Jiang-su province , the People ’s Republic of China . This area has the second highest rate of PLC in China . One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite ( Se-salt ) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt . The second trial was undertaken among hepatitis B virus surface antigen carriers ( HBVsAg+ ) receiving supplement of 200 μg Se in form of selenized , yeast ( Se-yeast ) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence  using Se-yeast ( 200 μg of Se daily ) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly BACKGROUND Although low dietary intakes of antioxidant vitamins and minerals have been associated with higher risks of cancer , results of trials testing antioxidant supplementation for cancer chemoprevention have been equivocal . We assessed whether supplementation with antioxidant vitamins could reduce the incidence of second primary cancers among patients with head and neck cancer . METHODS We conducted a multicenter , double-blind , placebo-controlled , r and omized chemoprevention trial among 540 patients with stage I or II head and neck cancer treated by radiation therapy between October 1 , 1994 , and June 6 , 2000 .  Supplementation with alpha-tocopherol ( 400 IU/day ) and beta-carotene ( 30 mg/day ) or placebo began on the first day of radiation therapy and continued for 3 years after the end of radiation therapy . In the course of the trial , beta-carotene supplementation was discontinued after 156 patients had enrolled because of ethical concerns . The remaining patients received alpha-tocopherol or placebo only .  Survival was evaluated by Kaplan-Meier analysis . Cox proportional hazards models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS After a median follow-up of 52 months , second primary cancers and recurrences of the first tumor were diagnosed in 113 and 119 participants , respectively . The effect of supplementation on the incidence of second primary cancers varied over time . Compared with patients receiving placebo , patients receiving alpha-tocopherol supplements had a higher rate of second primary cancers during the supplementation period ( HR = 2.88 , 95 % CI = 1.56 to 5.31 ) but a lower rate after supplementation was discontinued ( HR = 0.41 , 95 % CI = 0.16 to 1.03 ) . Similarly , the rate of having a recurrence or second primary cancer was higher during ( HR = 1.86 , 95 % CI = 1.27 to 2.72 ) but lower after ( HR = 0.71 , 95 % CI = 0.33 to 1.53 ) supplementation with alpha-tocopherol . The proportion of participants free of second primary cancer overall after 8 years of follow-up was similar in both arms . CONCLUSIONS alpha-Tocopherol supplementation produced unexpected adverse effects on the occurrence of second primary cancers and on cancer-free survival BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration BACKGROUND Several human studies have observed a direct association between retinol ( vitamin A ) intake and risk of prostate cancer ; other studies have found either an inverse association or no association of intake of beta-carotene ( the major provitamin A ) with risk of prostate cancer . Data regarding carotenoids other than beta-carotene in relation to prostate cancer risk are sparse . PURPOSE We concluded a prospect i ve cohort study to examine the relationship between the intake of various carotenoids , retinol , fruits , and vegetables and the risk of prostate cancer . METHODS Using responses to a vali date d , semiquantitative food-frequency question naire mailed to participants in the Health Professionals Follow-up Study in 1986 , we assessed dietary intake for a 1-year period for a cohort of 47,894 eligible subjects initially free of diagnosed cancer . Follow-up question naires were sent to the entire cohort in 1988 , 1990 , and 1992 . We calculated the relative risk ( RR ) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level . All P values result ed from two-sided tests . RESULTS Between 1986 and 1992 , 812 new cases of prostate cancer , including 773 non-stage A1 cases , were documented . Intakes of the carotenoids beta-carotene , alpha-carotene , lutein , and beta-cryptoxanthin were not associated with risk of non-stage A1 prostate cancer ; only lycopene intake was related to lower risk ( age- and energy-adjusted RR = 0.79 ; 95 % confidence interval [ CI ] = 0.64 - 0.99 for high versus low quintile of intake ; P for trend = .04 ) . Of 46 vegetables and fruits or related products , four were significantly associated with lower prostate cancer risk ; of the four -- tomato sauce ( P for trend = .001 ) , tomatoes ( P for trend = .03 ) , and pizza ( P for trend = .05 ) , but not strawberries -- were primary sources of lycopene . Combined intake of tomatoes , tomato sauce , tomato juice , and pizza ( which accounted for 82 % of lycopene intake ) was inversely associated with risk of prostate cancer ( multivariate RR = 0.65 ; 95 % CI = 0.44 - 0.95 , for consumption frequency greater than 10 versus less than 1.5 servings per week ; P for trend = .01 ) and advanced ( stages C and D ) prostate cancers ( multivariate RR = 0.47 ; 95 % CI = 0.22 - 1.00 ; P for trend = .03 ) . No consistent association was observed for dietary retinol and risk of prostate cancer . CONCLUSIONS These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk , but other measured carotenoids are unrelated to risk . IMPLICATION S Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk Selenium status has been inversely associated with  colorectal cancers ( CRC ) and adenomas  . This investigation evaluates the association between selenium supplementation and prevalent and incident colorectal adenomas and CRC detected during the Nutritional Prevention of Cancer trial follow-up . Of the 1,312 r and omized to 200 mcg of selenized yeast of matching placebo , 598 participants underwent endoscopic screening ( flexible sigmoidoscopy or colonoscopy ) for CRC sometime during the follow-up period , which ended in February 1 , 1996 . There was no colorectal screening performed at baseline . Of those screened , 77 % were male ( with a mean age of 62.8 years ) , 42 % were former and 25 % were current smokers .  Adenomas were classified as prevalent ( identified at the first endoscopic examination post-r and omization during the follow-up period ) or incident ( identified at the second or subsequent examination ) . Ninety-nine prevalent and 61 incident adenomas were ascertained . Logistic regression odds ratios ( OR ) and 95 % confidence intervals ( CI ) were calculated , adjusting for age , gender and smoking status . For prevalent adenomas , there was a suggestive but nonsignificant decrease in risk associated with selenium treatment ( OR = 0.67 , 95 % CI = 0.43 - 1.05 ) . Subjects in the lowest tertile of baseline selenium ( OR = 0.27 , 95 % CI = 0.09 - 0.77 ) and current smokers ( OR = 0.27 , 95 % CI = 0.11 - 0.66 ) had significant reductions in risk . The OR for incident adenomas was 0.98 ( 95 % CI = 0.57 - 1. 
    Output:
    
Beta carotene supplementation appeared to increase cancer incidence and cancer mortality among smokers , whereas vitamin E supplementation had no effect .