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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA107431-07
Application #
8152222
Study Section
Special Emphasis Panel (ZRG1-PSE-D (03))
Program Officer
Umar, Asad
Project Start
2004-04-01
Project End
2015-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
7
Fiscal Year
2011
Total Cost
$1,796,073
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Jasmine, Farzana; Shinkle, Justin; Sabarinathan, Mekala et al. (2018) A novel pooled-sample multiplex luminex assay for high-throughput measurement of relative telomere length. Am J Hum Biol 30:e23118
Argos, Maria; Tong, Lin; Roy, Shantanu et al. (2018) Screening for gene-environment (G×E) interaction using omics data from exposed individuals: an application to gene-arsenic interaction. Mamm Genome 29:101-111
Vogtmann, Emily; Chen, Jun; Kibriya, Muhammad G et al. (2017) Comparison of Fecal Collection Methods for Microbiota Studies in Bangladesh. Appl Environ Microbiol 83:
Surrette, Christine; Shoudy, David; Corwin, Alex et al. (2017) Microfluidic Tissue Mesodissection in Molecular Cancer Diagnostics. SLAS Technol 22:425-430
Kibriya, Muhammad G; Jasmine, Farzana; Parvez, Faruque et al. (2017) Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study. Environ Health 16:75
Chen, Yu; Wu, Fen; Saito, Eiko et al. (2017) Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia 60:1022-1032
Shih, Yu-Hsuan; Islam, Tariqul; Hore, Samar Kumar et al. (2017) Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality. Environ Res 158:456-461
Dean, Samantha G; Zhang, Chenan; Gao, Jianjun et al. (2017) The association between telomere length and mortality in Bangladesh. Aging (Albany NY) 9:1537-1551
Bulka, Catherine M; Davis, Matthew A; Karagas, Margaret R et al. (2017) The Unintended Consequences of a Gluten-free Diet. Epidemiology 28:e24-e25
Pesola, Gene R; Ahsan, Habibul (2016) Dyspnea as an independent predictor of mortality. Clin Respir J 10:142-52

Showing the most recent 10 out of 90 publications