Nearly 200 million people in the world including 40-70 million in Bangladesh have been exposed to arsenic from drinking water and thus at increased risk of skin and other cancers for their lifetime. The most likely mechanism underlying this arsenic-induced risk is oxidative stress mediated DNA and cellular damage. To identify an effective preventive approach for this increased risk we established the Bangladesh vitamin E and selenium Trial (BEST)-a 2W2 factorial randomized chemoprevention trial (RCT) for evaluating whether long- term vitamin E or selenium supplementation prevents non-melanoma skin cancer (NMSC) risk and alters oxidative stress markers in peripheral tissues in a uniquely exposed population. In 2005, we were awarded funding for the first 5 years of this 10-year study. The goal of the first funding period was to design BEST and identify, recruit, and randomize 4,444 individuals with arsenic-related skin lesions into 4 treatment arms: vitamin E only (100 IU/day), L-selenomethionine only (200 5g/day), both vitamin E and selenium, and placebo. To ensure the successful completion of the study, we have exceeded our recruitment target by 80% and randomized 7,000 individuals. In the proposed 5 years of the study (7/1/2010-6/30/2015), we will complete the study through continued intervention for 6 years, follow-up (including a post-intervention period), collection of questionnaire and clinical data, and biological samples at various time points, and finally statistical analyses and report writing of the final dataset. In view of current concerns regarding a possible diabetogenic effect of selenium supplementation, we now include a new specific aim to specifically assess treatment effects on that endpoint, in addition to our originally proposed endpoints of NMSC and mortality. Finally, as an extension of our ongoing evaluation of the current specific aim to examine treatment effects on oxidative stress markers, especially 8-OHdG, in peripheral tissues (blood and urine), we now also include an aim to more comprehensively and specifically evaluate treatment effects on a panel of oxidative stress markers measured in normal skin and NMSC tissues-the target tissues of our primary clinical endpoint. Overall, BEST will be a highly efficient and unique RCT, able to evaluate effects of vitamin E and selenium supplementation on prevention of skin cancer and other health outcomes and will create a valuable research resource for future prevention, clinical and molecular research.

Public Health Relevance

In order to identify effective preventive approach for arsenic-related increased cancer risk we propose to continue our 2W2 factorial randomized chemoprevention trial that we established during the last funding period for evaluating whether long-term vitamin E or selenium supplementation prevents non-melanoma skin cancer risk and alters oxidative stress markers in peripheral tissues in a uniquely exposed population. In addition to the original aims on skin cancer and mortality this current proposal also includes a new aim about the treatment effects on diabetes mellitus.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-PSE-D (03))
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Umar, Asad
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University of Chicago
Internal Medicine/Medicine
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United States
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Pesola, Gene R; Ahsan, Habibul (2016) Dyspnea as an independent predictor of mortality. Clin Respir J 10:142-52
Jansen, Rick J; Argos, Maria; Tong, Lin et al. (2016) Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity. Cancer Epidemiol Biomarkers Prev 25:381-90
Farzan, Shohreh F; Karagas, Margaret R; Jiang, Jieying et al. (2015) Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Toxicol Appl Pharmacol 288:95-105
Jiang, Jieying; Liu, Mengling; Parvez, Faruque et al. (2015) Association between Arsenic Exposure from Drinking Water and Longitudinal Change in Blood Pressure among HEALS Cohort Participants. Environ Health Perspect 123:806-12
Argos, Maria; Chen, Lin; Jasmine, Farzana et al. (2015) Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect 123:64-71
Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G et al. (2015) Interaction between arsenic exposure from drinking water and genetic polymorphisms on cardiovascular disease in Bangladesh: a prospective case-cohort study. Environ Health Perspect 123:451-7
Jiang, Jieying; Liu, Mengling; Parvez, Faruque et al. (2015) Association of major dietary patterns and blood pressure longitudinal change in Bangladesh. J Hypertens 33:1193-200
Gao, Jianjun; Roy, Shantanu; Tong, Lin et al. (2015) Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals. Environ Res 136:462-9
Pesola, Gene R; Argos, Maria; Chen, Yu et al. (2015) Dipstick proteinuria as a predictor of all-cause and cardiovascular disease mortality in Bangladesh: A prospective cohort study. Prev Med 78:72-7
Karagas, Margaret R; Gossai, Anala; Pierce, Brandon et al. (2015) Drinking Water Arsenic Contamination, Skin Lesions, and Malignancies: A Systematic Review of the Global Evidence. Curr Environ Health Rep 2:52-68

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