Carcinogenesis vol.32 no.10 pp.1500–1506, 2011 doi:10.1093/carcin/bgr139 Advance Access publication July 18, 2011
Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial Li Tang, Song Yao, Cathee Till1, Phyllis J.Goodman1, Catherine M.Tangen1, Yue Wu, Alan R.Kristal1, Elizabeth A.Platz2, Marian L.Neuhouser1, Frank Z.Stanczyk3, Juergen K.V.Reichardt4, Regina M.Santella5, Ann Hsing6, Ashraful Hoque7, Scott M.Lippman8, Ian M.Thompson9 and Christine B.Ambrosone Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA, 1Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA, 3Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, CA 90089, USA, 4School of Pharmacy and Molecular Sciences, James Cook University, Townsville QLD 4811, Australia, 5 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA, 6Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA, 7Department of Clinical Cancer Prevention, 8Department of Thoracic Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA and 9Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA To whom correspondence should be addressed. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Carlton House Room 342, Buffalo, NY 14263. Tel: þ1 716 845 8247; Fax: þ1 716 845 8487; Email:
[email protected]
The etiology of prostate cancer remains elusive, although steroid hormones probably play a role. Considering the carcinogenic potential of estrogen metabolites as well as altered intraprostatic estrogen biosynthesis during the development of prostate cancer, we investigated associations between repeat polymorphisms of three key estrogen-related genes (CYP11A1, CYP19A1, UGT1A1) and risk of prostate cancer in the Prostate Cancer Prevention Trial (PCPT), designed to test finasteride versus placebo as a chemoprevention agent. Using data and specimens from 1154 cases and 1351 controls who were frequency matched on age, family history of prostate cancer and PCPT treatment arm, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) separately in the placebo and finasteride arms. Among men in the placebo arm, CYP19A1 7/8 genotype carriers had a significantly higher risk of prostate cancer compared with those with the 7/7 genotype (OR 5 1.70, 95% CI 5 1.16–2.5), regardless of Gleason grade. This genotype was also associated with elevated serum estrogen levels. For the (TA)n repeat polymorphism in UGT1A1, the heterozygous short (
