Demetrius Albanes, M.D.
Metabolic Epidemiology Branch
9609 Medical Center Drive
Rockville, MD 20850
Dietary and nutritional exposures have long been thought related to population and individual differences in cancer rates and risk, yet much remains unknown regarding specific cause and effect relationships and biological mechanisms. We are conducting a population-based, epidemiologic research program of observational studies and controlled trials to investigate the etiologic role of nutritional, biochemical/molecular, and other factors in prostate, lung, colorectal and other cancers. Of particular interest are the effects of micronutrients - for example, carotenoids, tocopherols (vitamin E), selenium, and folate - and energy-related exposures such as caloric intake, anthropometry, and physical activity, with the overall objective of identifying preventive interventions and strategies for cancer.
Effects of ß-Carotene and α-Tocopherol Supplementation
We studied the effectiveness of long-term supplementation with ß-carotene and α-tocopherol (vitamin E) for preventing lung, prostate, and other cancers in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study of 29,133 50- to 69-year-old male smokers. This landmark trial was the first to show that supplemental ß-carotene might not prevent cancer and that it could adversely affect lung carcinogenesis in smokers. Within this cohort, we are testing hypotheses relevant to how ß-carotene supplementation may have promoted cancer, including effects on peripheral and/or tumor cytochrome-p450 activity, oxidation products, PAH adducts, RAR/RXR expression, DNA methylation, and cell proliferation/apoptosis. Ongoing surveillance of the ATBC cohort is examining post-intervention cancer incidence trends for the ß-carotene, α-tocopherol, and placebo groups in order to delineate the long-term effects of supplementation.
A substantial prostate cancer inhibitory effect for vitamin E (α-tocopherol) supplementation was also shown in our trial, with 32 and 41 percent reductions in incidence and mortality, respectively, over a 5-8 year period. Significant progress has been made in systematically testing the mechanisms through which vitamin E acted to prevent clinical prostate cancer, such as modulation of hormones and growth factors, including testosterone and IGF-1. Preliminary data show that circulating androgens were reduced by vitamin E, for example. Given the magnitude and public health implications of the main finding, we are collaborating with the Southwest Oncology Group on a confirmatory study of these hypotheses through a large, multicenter, phase III trial (SELECT) of supplementation with vitamin E (400 IU/day) and selenium (200 µg/day) in prostate cancer prevention.
Micronutrients and Genetic Polymorphisms
The role of various micronutrients, and their interactions with several relevant genetic polymorphisms, have been investigated based on prospectively collected serum, genomic DNA, tumor tissue, and high-quality epidemiologic data including dietary intake. Analyses of vitamins A, B6 and B12, C, D, and E, carotenoids, folate, selenium and other trace elements, androgens, and insulin-like growth factors and binding proteins have focused on lung, prostate, and large bowel cancers in particular, with some attention also on cancers of the pancreas, stomach, and bladder. Studies of genetic polymorphisms relevant to the metabolism and function of nutrients, growth factors, and hormones (e.g., MTHFR, IGF1, SRD5α2) and to carcinogen activation/elimination (e.g., GSTM1 and CYP1A1) are testing both their direct associations with cancer as well as their interactions with the trial interventions and other important exposures relevant to cancer. For example, under study is the role of several genetic polymorphisms potentially relevant to prostate carcinogenesis, and to the α-tocopherol preventive effect, including those relevant to sex hormone metabolism and function, such as SRD5α2, HSD3ß2, CYP17, and AR. Gene functionality is being evaluated through analysis of serum steroid hormones vis-a-vis the gene variants. Our discovery of an α-tocopherol effect on serum testosterone and androstenedione makes investigation of this area particularly timely in order to determine whether vitamin E directly affects androgen synthesis, release or clearance, or inhibits cell proliferation and induces apoptosis in the prostate. These studies are based on large numbers of cumulatively diagnosed cancers in the cohort; for example, approximately 1800 lung, 800 prostate, 350 colorectal, 350 bladder, 200-250 each for stomach, pancreas, and kidney cancers.
Based on experimental data identifying a strong cancer preventive effect of energy restriction and/or increased energy expenditure, and epidemiologic studies of cancer risk associated with diet, anthropometry, and physical activity, we also continue to investigate the relationship between body size and physical activity and several cancers, including breast cancer.
Dr. Albanes received his B.S. in biology from the State University of New York at Stony Brook and his M.D. from the Medical College of Wisconsin. After completing his internship at the University of California, Irvine, he joined the Epidemic Intelligence Service of the Centers for Disease Control (CDC), through which he began working in the cancer prevention program of the NCI in 1982. Thereafter, Dr. Albanes completed a preventive medicine residency with the CDC and continued his research in the Cancer Prevention Studies Branch of NCI from 1984 to 1990, when he became a tenured senior investigator. He was awarded the Public Health Service Commendation Medal in 1992 for his research and leadership in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, and joined the Division of Cancer Epidemiology and Genetics in 2000 as a senior investigator in the Nutritional Epidemiology Branch. He served as Chief of the Office of Education until 2008.
Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010;19(13):2739-45.
Weinstein SJ, Mondul AM, Kopp W, Rager H, Virtamo J, Albanes D. Circulating 25-hydroxyvitamin D, vitamin D-binding protein and risk of prostate cancer. Int J Cancer. 2013;132(12):2940-7.
Mondul AM, Shui IM, Yu K, Travis RC, Stevens VL, Campa D, Schumacher FR, Ziegler RG, Bueno-de-Mesquita HB, Berndt S, Crawford ED, Gapstur SM, Gaziano JM, Giovannucci E, Haiman CA, Henderson BE, Hunter DJ, Johansson M, Key TJ, Le Marchand L, Lindström S, McCullough ML, Navarro C, Overvad K, Palli D, Purdue M, Stampfer MJ, Weinstein SJ, Willett WC, Yeager M, Chanock SJ, Trichopoulos D, Kolonel LN, Kraft P, Albanes D. Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium. Cancer Epidemiol Biomarkers Prev. 2013;22(4):688-96.
Albanes D, Till C, Klein EA, Goodman PJ, Mondul AM, Weinstein SJ, Taylor PR, Parnes HL, Gaziano JM, Song X, Fleshner NE, Brown PH, Meyskens FL Jr, Thompson IM. Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Prev Res (Phila). 2014;7(9):886-95.
Mondul AM, Moore SC, Weinstein SJ, Karoly ED, Sampson JN, Albanes D. Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha-tocolpherol, beta-carotene cancer prevention (ATBC) study. Int J Cancer. 2015;137(9):2124-32.
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This page was last updated on July 18th, 2016