***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: In many observational studies , a higher intake of individual antioxidants is inversely associated with  lung cancer risk . Data from in vitro and animal experiments suggest that there are biochemical interactions among antioxidant nutrients ; therefore , consideration of multiple antioxidants simultaneously may be important in terms of risk estimation . The authors constructed a dietary antioxidant index and evaluated its ability to predict lung cancer risk within the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study cohort . At baseline ( 1985 - 1988 ) , 27,111 Finnish male smokers aged 50 - 69 years completed a dietary question naire that assessed usual frequency of consumption and portion sizes for the previous 12 months . A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years ( 1985 - 1999 ) . Principal components analyses were individually applied to the carotenoid , flavonoid , and vitamin E nutrient groups , and summation of retained principal component scores , plus selenium and vitamin C , yielded the composite antioxidant index . In multivariate proportional hazards models , the relative risks for lung cancer according to increasing quintiles of the antioxidant index were 1.00 ( referent ) , 1.00 ( 95 % confidence interval ( CI ) : 0.87 , 1.14 ) , 0.91 ( 95 % CI : 0.79 , 1.05 ) , 0.79 ( 95 % CI : 0.68 , 0.92 ) , and 0.84 ( 95 % CI : 0.72 , 0.98 ) ( p for trend = 0.002 ) . These findings support the hypothesis that a combination of dietary antioxidants reduces lung cancer risk in male smokers Oxidative stress may enhance prostatic carcinogenesis . A polymorphism [ valine ( V ) -- > alanine ( A ) ] of manganese superoxide dismutase ( MnSOD ) , the primary antioxidant enzyme in mitochondria , has been recently associated with prostate cancer . We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels ( selenium , lycopene , and alpha-tocopherol ) and beta-carotene treatment among 567 cases and 764 controls nested in the prospect i ve Physicians ' Health Study . We found little overall association between MnSOD polymorphism and prostate cancer risk ; however , this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants ( P(interaction ) > or = 0.05 ) . Among men with the AA genotype , high selenium level ( 4th versus 1st quartile ) was associated with a relative risk ( RR ) of 0.3 [ 95 % confidence interval ( CI ) , 0.2 - 0.7 ] for total prostate cancer ; for clinical ly aggressive prostate cancer , the RR was 0.2 ( 95 % CI , 0.1 - 0.5 ) . In contrast , among men with the VV/VA genotype , the RRs were 0.6 ( 0.4 - 1.0 ) and 0.7 ( 0.4 - 1.2 ) for total and clinical ly aggressive prostate cancer . These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined ; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status . Men with AA genotype who were r and omly assigned to beta-carotene treatment ( versus placebo ) had a RR of 0.6 ( 95 % CI , 0.2 - 0.9 ; P(interaction ) = 0.03 ) for fatal prostate cancer , but no significant association was observed in men with the VV/VA genotype . Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinical ly significant prostate cancer BACKGROUND Multivitamin supplements are used by millions of Americans because of their potential health benefits , but the relationship between multivitamin use and prostate cancer is unclear . METHODS We prospect ively investigated the association between multivitamin use and risk of prostate cancer ( localized , advanced , and fatal ) in 295,344 men enrolled in the National Institutes of Health (NIH)-AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996 . During 5 years of follow-up , 10,241 participants were diagnosed with incident prostate cancer , including 8765 localized and 1476 advanced cancers . In a separate mortality analysis with 6 years of follow-up , 179 cases of fatal prostate cancer were ascertained . Multivitamin use was assessed at baseline as part of a self-administered , mailed food-frequency question naire .  Relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were calculated by use of Cox proportional hazards regression , adjusted for established or suspected prostate cancer risk factors . RESULTS No association was observed between  multivitamin use and risk of localized prostate cancer . However , we found an increased risk of advanced and fatal prostate cancers ( RR = 1.32 , 95 % CI = 1.04 to 1.67 and RR = 1.98 , 95 % CI = 1.07 to 3.66 , respectively ) among men reporting excessive use of multivitamins  ( more than seven times per week ) when compared with never users . The incidence rates per 100,000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9 , respectively , compared with 113.4 and 11.4 in never users . The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements , including selenium , beta-carotene , or zinc . CONCLUSION These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer . The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation Interest in the chemopreventive effects of the trace element selenium has spanned the past three decades . Of > 100 studies that have investigated the effects of selenium in carcinogen-exposed animals , two-thirds have observed a reduction in tumor incidence and /or preneoplastic endpoints ( G. F. Combs and S. B. Combs , The Role of Selenium in Nutrition Chapter 10 , pp . 413 - 462 . San Diego , CA : Academic Press , 1986 , and B. H. Patterson and O. A. Lev and er , Cancer Epidemiol . Biomark . Prev . , 6 : 63 - 69 , 1997 ) . The Nutritional Prevention of Cancer Trial , a r and omized clinical trial reported by Clark et al. ( L. C. Clark et al. , JAMA , 276 : 1957 - 1963 , 1996 ) , showed as a secondary end point , a statistically significant decrease in lung cancer incidence with selenium supplementation . The adjusted hazard ratio ( HR ) was 0.56 [ 95 % confidence interval ( CI ) , 0.31 - 1.01 ; P = 0.05 ] . These results were based on active follow-up of 1312 participants . This re analysis used an extended Nutritional Prevention of Cancer Trial participant follow-up through the end of the blinded clinical trial on February 1 , 1996 . The additional 3 years added 8 cases to the selenium-treated group and 4 cases to the placebo group , and increased follow-up to 7.9 years . The relative risk of 0.70 ( 95 % CI , 0.40 - 1.21 ; P = 0.18 ) is not statistically significant . Whereas the overall adjusted HR is not significant ( HR = 0.74 ; 95 % CI , 0.44 - 1.24 ; P = 0.26 ) , and the HR for current and former smokers was not significant , the trend is toward a reduction in risk of incident lung cancer with selenium supplementation . In a subgroup analysis there was a nominally significant HR among subjects with baseline plasma selenium in the lowest tertile ( HR = 0.42 ; 95 % CI , 0.18 - 0.96 ; P = 0.04 ) . The analysis for the middle and highest tertiles of baseline showed HRs of 0.91 and 1.25 . The current re analysis indicates that selenium supplementation did not significantly decrease lung cancer incidence in the full population , but a significant decrease among individuals with low baseline selenium concentrations was observed BACKGROUND Selenium is a potential chemopreventive agent against prostate cancer , whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes . Interrelations with other antioxidative agents and oxidative stressors , such as smoking , are poorly understood . OBJECTIVES The aims were to investigate the association between serum  selenium  and prostate cancer risk and to examine interactions with other antioxidants and tobacco use . DESIGN A nested case-control study was performed within the screening arm of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial .  Serum selenium  in prospect ively collected sample s was compared between 724 incident prostate cancer case subjects and 879 control subjects , frequency-matched for age , time since initial screen , and year of blood draw . The men were followed for up to 8 y. RESULTS Overall , serum selenium was not associated with prostate cancer risk ( P for trend = 0.70 ) ; however , higher serum selenium was associated with lower risks in men reporting a high ( more than the median : 28.0 IU/d ) vitamin E intake [ odds ratio ( OR ) for the highest compared with the lowest quartile of selenium : 0.58 ; 95 % CI : 0.37 , 0.91 ; P for trend = 0.05 ; P for interaction = 0.01 ] and in multivitamin users ( OR for highest compared with the lowest quartile of selenium : 0.61 ; 95 % CI : 0.36 , 1.04 ; P for trend = 0.06 ; P for interaction = 0.05 ) . Furthermore , among smokers , high serum selenium concentrations were related to reduced prostate cancer risk ( OR for the highest compared with the lowest quartile of selenium : 0.65 ; 95 % CI : 0.44 , 0.97 ; P for trend = 0.09 ; P for interaction = 0.007 ) . CONCLUSION Greater prediagnostic serum selenium concentrations were not associated with prostate cancer risk in this large cohort , although greater concentrations were associated with reduced prostate cancer risks in men who reported a high intake of vitamin E  , in multivitamin users , and in smokers The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( n = 29,133 ) . During up to 9 years of follow-up , 317 men developed incident prostate cancer . Multivariate Cox proportional hazards models that adjusted for intervention group , benign prostatic hyperplasia , age , smoking , and urban residence were used to evaluate associations between prostate cancer and exposures of interest . There were no significant associations between baseline serum alpha-tocopherol , dietary vitamin E , or selenium and prostate cancer overall . The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status , with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention ( relative risk was 1.00 , 0.68 , 0.80 , and 0.52 for increasing quartiles ; P = 0.07 ) Nonexperimental studies suggest that individuals with higher selenium ( Se ) status are at decreased risk of cancer . The Nutritional Prevention of Cancer ( NPC ) study r and omized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo ; selenium supplementation decreased the risk of lung , colon , prostate , and total cancers but increased the risk of nonmelanoma skin cancer . In this article , we report on a small sub study in Macon , GA , which began in 1989 and r and omized 424 patients to 400-mcg/day of Se or to matched placebo .  The subjects from both arms had similar baseline Se levels to those treated by 200 mcg , and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg . The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25 % ; however , 400-mcg/day of Se had no effect on total cancer incidence 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 Linx 
    Output:
    
RCTs with low risk of bias suggested increased melanoma risk .
Results for most outcomes were similar when we included all RCTs in the meta- analysis , regardless of risk of bias .
Summary RRs for site-specific cancers showed limited changes compared with estimates from high- quality studies alone , except for liver cancer , for which results were reversed .
No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies .Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types , but null and direct relations have also been reported , and no systematic pattern suggesting dose-response relations has emerged .
Overall , there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans .