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Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

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Abstract

Objective: To conduct timely epidemiologic investigations of molecular/genetic markers that may contribute to the development of prostate, lung, colorectal, 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 men aged 55 years or older (age 50 or older for the African-American men) enrolled into an intergroup, randomized, placebo-controlled, double-blind, phase III prevention trial of supplemental selenium and vitamin E developed and funded by the National Cancer Institute, and coordinated by the Southwest Oncology Group. During the 12-year study period approximately 1500–2000 cases of prostate cancer, 800 lung cancers, and 500 colon cancers are estimated to be diagnosed, based on data from the ongoing Prostate Cancer Prevention 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 lines. Red blood cells will be stored for analysis of hemoglobin adducts and other components.

Results: Specific results anticipated from these molecular studies will provide information on factors hypothesized to contribute to prostate cancer risk and that may modify the efficacy of either trial supplement, including: steroid sex hormones and several polymorphic genes that encode proteins affecting androgenic stimulation of the prostate, including the androgen receptor, steroid 5α-reductase type II, CYP17, and β-hydroxysteroid dehydrogenase; polymorphisms of DNA repair genes and carcinogen metabolism genes, including those involved in the activation of chemical carcinogens to reactive intermediates (e.g., CYP1A1) or the detoxification of reactive intermediates (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 epidemiologic investigations to assess gene–environment interactions and their role in prostate, lung, and colon carcinogenesis.

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Authors and Affiliations

  1. Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA

    Ashraful Hoque & Scott M. Lippman

  2. Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland, 20892, USA

    Demetrius Albanes & Phillip R. Taylor

  3. Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA

    Margaret R. Spitz

  4. Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA

    Eric A. Klein

  5. Division of Urology, University of Texas Health Science Center at San Antonio, Texas, 78284, USA

    Ian M. Thompson

  6. Southwest Oncology Group Statistical Center, Seattle, Washington, 98109, USA

    Phyllis Goodman & John J. Crowley

  7. Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, USA

    Janet L. Stanford

  8. Southwest Oncology Group, San Antonio, Texas, 78245, USA

    Charles A. Coltman

  9. Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, New York, 10032, USA

    Regina M. Santella

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  1. Ashraful Hoque
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Hoque, A., Albanes, D., Lippman, S.M. et al. Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Causes Control 12, 627–633 (2001). https://doi.org/10.1023/A:1011277600059

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