***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: Abnormalities of epithelial proliferation have been proposed as an early step in gastrointestinal carcinogenesis . To determine whether micronutrient supplementation may reduce squamous epithelial proliferation in the esophagus , we evaluated proliferation in subjects participating in a r and omized nutrition intervention trial in Linxian , China , where esophageal cancer rates are among the highest in the world . After 30 months of intervention involving daily supplementation with multiple vitamins and minerals , an endoscopic survey was performed and squamous biopsies from 512 subjects were labeled with tritiated thymidine and autoradiographed . Analysis showed no treatment effect on the overall amount of squamous epithelial proliferation measured by the total labeling index . However , a measure of the vertical distribution of labeled cells showed lower values with supplementation : a 14 % reduction in all subjects ( P = 0.29 ) , and a 29 % reduction in nonsmokers ( P = 0.03 ) . These results suggest a potential modest benefit for short-term intervention with multiple vitamins and minerals on squamous epithelial cell proliferation of the esophagus in this high-risk population Data from a double-blind intervention trial in China are reanalyzed to explore auxiliary information . The trial had shown that in a high-risk area for esophageal cancer the dietary supplementation of apparently healthy individuals with a combination of retinol , riboflavin , and zinc did not lead to a different prevalence of precancerous lesions of the esophagus among those receiving the active treatment compared to a placebo group . However , improvement of blood retinol and zinc levels were also observed in the placebo group . The logistic regression analysis presented in this paper illustrates that those individuals who showed large increases in retinol , riboflavin , and zinc blood levels were more likely to have a histologically normal esophagus at the end of the trial . This effect is clearer for retinol than for riboflavin and zinc and it is independent of whether the change was caused by the active treatment or occurred otherwise Linxian , China has some of the highest rates of esophageal/gastric cardia cancer in the world , and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates . To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population , a two-arm r and omized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia . During the 6-year intervention , esophageal/gastric cardia cancer mortality was 8 % lower among those receiving the active supplements . After 30 and 72 months of intervention , endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinical ly silent precancerous lesions and early invasive cancers of the esophagus and stomach . In the first survey , in 1987 , 833 subjects were endoscoped ; in the second survey , in 1991 , 396 subjects were examined . The histological diagnoses from each survey were compared by treatment group . Cancer or dysplasia was diagnosed in 28 % of the subjects endoscoped in 1987 and 24 % of those examined in 1991 . The odds ratio for subjects in the treatment group ( versus those in the placebo group ) having esophageal or gastric dysplasia or cancer was 0.84 ( 95 % confidence interval , 0.61 - 1.15 ) in 1987 and 0.86 ( 0.54 - 1.38 ) in 1991 . Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys , none of the results was statistically significant , and the findings must be considered inconclusive . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The General Population Nutrition Intervention Trial was a r and omized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991 , in which 29,584 adult participants in Linxian , China , were given daily vitamin and mineral supplements . Treatment with " factor D , " a combination of 50 microg selenium , 30 mg vitamin E , and 15 mg beta-carotene , led to decreased mortality from all causes , cancer overall , and gastric cancer . Here , we present 10-year follow-up after the end of active intervention . METHODS Participants were assessed by periodic data collection , monthly visits by village health workers , and quarterly review of the Linxian Cancer Registry . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models . RESULTS Through May 31 , 2001 , 276 participants were lost to follow-up ; 9727 died , including 3242 from cancer ( 1515 from esophageal cancer and 1199 from gastric cancer ) . Participants who received factor D had lower overall mortality ( HR = 0.95 , 95 % CI = 0.91 to 0.99 ; P = .009 ; reduction in cumulative mortality from 33.62 % to 32.19 % ) and gastric cancer mortality ( HR = 0.89 , 95 % CI = 0.79 to 1.00 ; P = .043 ; reduction in cumulative gastric cancer mortality from 4.28 % to 3.84 % ) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years . Esophageal cancer deaths between those who did and did not receive factor D were not different overall ; however , decreased 17 % among participants younger than 55 ( HR = 0.83 , 95 % CI = 0.71 to 0.98 ; P = .025 ) but increased 14 % among those aged 55 years or older ( HR = 1.14 , 95 % CI = 1.00 to 1.30 ; P = .047 ) [ corrected ] . Vitamin A and zinc supplementation was associated with increased total and stroke mortality ; vitamin C and molybdenum supplementation , with decreased stroke mortality . CONCLUSION The beneficial effects of selenium , vitamin E , and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants . Late effects of other supplementation regimens were also observed A nutrition intervention trial involving > 3000 participants was conducted in Linxian , China , where the esophageal and stomach cancer mortality rates are among the highest in the world and suspicion exists that chronic deficiencies of multiple nutrients are etiologically involved . The trial was r and omized , double-blind , and placebo-controlled and tested the effect of multivitamin and multimineral supplements in reducing cancer incidence and mortality in adults with cytologically detected esophageal dysplasia . Endoscopic and cytologic examinations of sample s of trial participants during the intervention allowed evaluation of intermediate endpoints in esophageal and gastric carcinogenesis , including asymptomatic histologic precancerous lesions and early invasive cancer , epithelial proliferation , and cytologic abnormalities . Results from these ancillary studies suggest that multivitamin and multimineral supplementation may decrease proliferation and enhance cytologic reversion to nondysplasia The people of Linxian County , China have one of the world 's highest rates of esophageal cancer . Two intervention trials were conducted to determine whether supplementation with specific vitamins and minerals could lower mortality from or incidence of cancer in this population and whether supplementation with multiple vitamins and minerals would reduce esophageal and gastric cardia cancer in persons with esophageal dysplasia . About 30,000 general population ( GP ) subjects in the GP trial were r and omly assigned to one of eight intervention groups according to a one-half replicate of a 2(4 ) factorial experimental design and were supplemented for 5.25 y with four combinations of micronutrients at doses from one to two times the US recommended dietary allowance ( RDA ) . About 3000 subjects in whom dysplasia was diagnosed in the dysplasia trial were r and omly assigned to groups receiving daily supplementation with 14 vitamins and 12 minerals at two to three times the US RDA or placebo for 6 y. Results of the dysplasia trial indicate that in individuals with esophageal dysplasia , micronutrient supplementation had little effect on T lymphocyte responses . In contrast , male participants in the GP trial who were supplemented with beta-carotene , vitamin E , and selenium showed significantly ( P < 0.05 ) higher mitogenic responsiveness of T lymphocytes in vitro than those not receiving these micronutrients A r and omized nutrition intervention trial was conducted among 29,584 adult residents of Linxian , China , to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population . A fractional factorial study design allowed evaluations of four different combinations of nutrients : ( A ) retinol and zinc ; ( B ) riboflavin and niacin ; ( C ) vitamin C and molybdenum ; and ( D ) beta-carotene , vitamin E , and selenium . During the 5.25-year intervention , significant reductions in total mortality , total cancer mortality , and stomach cancer mortality occurred among those receiving beta-carotene , vitamin E , and selenium . At the end of intervention , an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinical ly silent precancerous lesions and early invasive cancers of the esophagus or stomach . Endoscopy was performed on 391 individuals from two study villages . The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor . Cancer or dysplasia was diagnosed in 15 % of the participants . No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations . The greatest reduction in risk ( odds ratio , 0.38 ; P = 0.09 ) was seen for the effect of retinol and zinc on the prevalence of gastric cancer . Although no significant protective effects were seen in this endoscopic survey , there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population . Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility BACKGROUND In rodents , zinc deficiency potentiates the effects of certain nitrosamines that act as esophageal carcinogens . Studies of the association between zinc and esophageal squamous cell carcinoma in humans have been hampered by plasma zinc homeostasis , which obscures individual differences in total zinc stores , and by the uncertainty regarding zinc bioavailability when estimating dietary zinc intake because phytate from whole grains effectively prohibits zinc absorption . By using baseline tissue biopsy specimens collected in a prospect i ve observational study , we determined the association between incident esophageal squamous cell carcinoma and baseline element concentrations in tissue sections from residents of Linzhou , China , participating in a nutrition intervention trial . METHODS We used x-ray fluorescence spectroscopy to measure zinc , copper , iron , nickel , and sulfur concentrations in single 5-microm-thick sections from  formalin-fixed , paraffin-embedded esophageal biopsy specimens collected in 1985 from 60 eventual case and 72 control subjects . Subjects were matched on baseline histology and followed for 16 years . We used Cox proportional hazards models to estimate the hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the association between each element and risk of incident esophageal cancer . All statistical tests were two-sided . RESULTS The risk of developing esophageal cancer was much lower for subjects in the highest quartile of esophageal tissue zinc concentration compared with those in the lowest quartile ( HR = 0.21 , 95 % CI = 0.065 to 0.68 ) . The association was statistically significant across quartiles ( P(trend ) = .015 ) . Individuals in the highest quartile of sulfur concentration had a lower risk of esophageal cancer than individuals in the lowest quartile ( HR = 0.29 , 95 % CI = 0.095 to 0.85 ) , but the association across quartiles was not statistically significant ( P(trend ) = .081 ) . There was no association between copper , iron , or nickel concentrations and risk of esophageal cancer . CONCLUSION High tissue zinc concentration was strongly associated with a reduced risk of developing esophageal squamous cell carcinoma . X-ray fluorescence spectroscopy can be used to assess relationships among concentrations of both nutritional and toxic elements and disease risk in banked tissue specimens Trace elements have been cited as both inhibitory and causative agents of cancer but importantly exposure to them is potentially modifiable . Our study aim ed to examine  toenail trace element status and risk of  Barrett 's oesophagus ( BO ) and oesophageal adenocarcinoma ( OAC ) . 
    Output:
    
The majority of studies suggested that higher zinc status was inversely associated with EC risk .
However , the evidence is not still strong enough to conclude a protective role of zinc in EC