Chemoprevention of arsenic induced skin cancer

We propose a double blind, randomized, placebo-controlled clinical trial to examine whether vitamin E and selenium have a beneficial effect on arsenic-induced skin lesions. 4,444 patients with confirmed arsenical skin lesions will be recruited from the Health Effects of Arsenic Longitudinal Study (HEALS), from a study population in and around Araihazar, and from the study population in and around Matlab. Potential subjects have already been identified in the Columbia and ICDDR,B databases. Participants will be randomly assigned in a 2x2 factorial design to one of four arms: alpha-tocopherol (100 mg daily), l-selenomethionine (200 µg daily), vitamin E and selenium (combination), or placebo. Treatment and follow-up will be for 5 years. Recruitment will proceed simultaneously at both study sites, and will be completed within 10-12 months. Complete physical examinations will be performed at five time points. Blood sample collection for measurement serum alpha-tocopherol, selenium and carotenoids will be done at 3 time points (baseline, 36 months, and 60 months). Efficacy will be determined by assessing the incidence of Squamous Cell Carconoma (SCC) and Basal Cell Carconoma (BCC), by evaluating changes in the mononuclear 8OHdG levels, and by evaluating changes of clinical features of arsenical skin lesions, including change in prevalent lesions and incidence of new ones. Selenium and alpha-tocopherol levels will be used as measures of study compliance; baseline carotenoid levels will be used as a covariate in the final analysis. Information on food habits will also be collected at 3 time points corresponding to biological sample collection to provide supplementary information on dietary status of the patients.