Molecular epidemiologic studies within the selenium and vitamin e cancer prevention trial (SELECT)

Objective: To conduct timely epidemiologic investigations of molecular/gene tic markers that may contribute to the development of prostate, lung, color ectal, or other cancers within the Selenium and Vitamin E Cancer Prevention Trial (SELECT), and to evaluate interactions between these markers and the study interventions. Methods: The epidemiologic studies within SELECT will be based on 32,400 me n aged 55 years or older (age 50 or older for the African-American men) enr olled into an intergroup, randomized, placebo-controlled, double-blind, pha se III prevention trial of supplemental selenium and vitamin E developed an d funded by the National Cancer Institute, and coordinated by the Southwest Oncology Group. During the 12-year study period approximately 1500-2000 ca ses of prostate cancer, 800 lung cancers, and 500 colon cancers are estimat ed to be diagnosed, based on data from the ongoing Prostate Cancer Preventi on Trial of finasteride. A modified fasting blood sample will be processed to collect plasma for analysis of micronutrients, hormones, cytokines, and other proteins. Buffy-coat derived white blood cells collected at baseline will be used for isolation of DNA and establishment of immortalized cell li nes. Red blood cells will be stored for analysis of hemoglobin adducts and other components. Results: Specific results anticipated from these molecular studies will pro vide information on factors hypothesized to contribute to prostate cancer r isk and that may modify the efficacy of either trial supplement, including: steroid sex hormones and several polymorphic genes that encode proteins af fecting androgenic stimulation of the prostate, including the androgen rece ptor, steroid 5 alpha -reductase type II, CYP17, and beta -hydroxysteroid d ehydrogenase; polymorphisms of DNA repair genes and carcinogen metabolism g enes, including those involved in the activation of chemical carcinogens to reactive intermediates (e.g., CYP1A1) or the detoxification of reactive in termediates (e.g., glutathione S-transferase M1); DNA and protein adducts; and insulin-like growth factors and leptin. Conclusion: SELECT offers an excellent opportunity to conduct molecular epi demiologic investigations to assess gene-environment interactions and their role in prostate, lung, and colon carcinogenesis.