Biography

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 and served as Chief of the Office of Education until 2008.

Research Interests

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, SRD5"2) 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 SRD5"2, HSD3$2, 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.

Keywords

androgens, anthropometry, carotenoids, colorectal cancer, cohort studies, diet-gene interactions, folate, genetic polymorphisms, insulin-like growth factors, intervention studies, lung cancer, molecular epidemiology, pancreatic cancer, physical activity, prostate cancer, selenium, tocopherols, vitamin E

Selected Publications

• Heinonen OP, et al. "Prostate cancer and supplementation with α-tocopherol and ß-carotene: incidence and mortality in a controlled trial." J Natl Cancer Inst 1998; 90:440-446.
• Albanes D, et al. "Effects of supplemental α-tocopherol and ß-carotene on colorectal cancer: results from a controlled trial (Finland)." Cancer Causes Control 2000; 11:197-205.
• Hartman TJ, et al. Effects of α-tocopherol supplementation on serum sex hormones in older men. Prostate 2001; 46:33-38.
• Stolzenberg-Solomon R, et al. "Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers." Am J Epidemiol 2001; 153:680-687.

Collaborators

DCEG Collaborators

• Dalsu Baris, M.D., Ph.D.; Erin Bell, Ph.D.; Neil Caporaso, M.D.; Anand Chokkalingham, Ph.D.; Wong-Ho Chow, Ph.D.; Eric Engels, M.D., M.P.H., D. Michal Freedman, Ph.D., M.P.H.; Patricia Hartge, Sc.D.; Richard Hayes, D.D.S., Ph.D., M.P.H.; Robert Hoover, M.D., Sc.D.; Ulrike Peters, Ph.D.; Nathaniel Rothman, M.D., M.P.H., M.S.; Catherine Schairer, Ph.D.; Arthur Schatzkin, M.D., Dr.P.H.; Rachael Stolzenberg-Solomon, Ph.D., M.P.H.; Tara Vogt, Ph.D.; Regina Ziegler, Ph.D.

Other NCI Collaborators

• Paul Albert, Ph.D.; Noreen Aziz, M.D., Ph.D.; Narayan Bhat, Ph.D.; Kenneth Buetow, Ph.D.; Anne Hartman, M.S.; William Kopp, Ph.D.; Peter McCarron, Ph.D.; Philip Taylor, M.D., Sc.D.; Karen Woodson, Ph.D., M.P.H.

Other Scientific Collaborators

• Georg Alfthan, Ph.D.; Jussi Huttunen, M.D.; Pasi Korhonen, Ph.D.; Nea Malila, M.D., Ph.D.; Pirjo Pietinen, Ph.D.; Jarmo Virtamo, M.D., National Public Health Institute, Helsinki, Finland
• Martin Blaser, M.D., Vanderbilt University, Nashville, TN
• June Chan, Ph.D.; David Hunter, M.B.B.S., Sc.D.; Walter Willett, M.D., Dr.P.H., Harvard School of Public Health, Boston, MA
• Charles Coltman, Jr., M.D., Southwest Oncology Group, San Antonio, TX
• Elaine Gunter, Ph.D., Centers for Disease Control and Prevention, Atlanta, GA
• Terryl Hartman, Ph.D., M.P.H., Pennsylvania State University, State College, PA
• Olli Heinonen, M.D., Sc.D., University of Helsinki, Finland
• Ari Hirvonen, Ph.D.; Kirsti Husgafvel, Ph.D., Finnish Institute of Occupational Health, Helsinki, Finland
• Irena King, Ph.D.; Alan Kristal, Ph.D., Fred Hutchinson Cancer Research Center, Seattle, WA
• Paul Limburg, M.D., M.P.H., Mayo Clinic, Rochester, MN
• Scott Lippman, M.D., M.D. Anderson Cancer Center, Houston, TX
• Joel Mason, M.D.; Jacob Selhub, Ph.D., Tufts University School of Medicine, Boston, MA
• Michael Pollak, M.D., Ph.D., McGill University, Montreal, Canada
• Eero Pukkala, Ph.D.; Lyly Teppo, M.D., Finnish Cancer Registry, Helsinki, Finland
• Elio Riboli, M.D., International Agency for Cancer Research, Lyon, France
• Regina Santella, Ph.D., Columbia University, New York, NY
• Ian Thompson, M.D., University of Texas Health Science Center at San Antonio, TX