TY - JOUR
T1 - Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk
T2 - Results from the Prostate Cancer Prevention Trial
AU - Tang, Li
AU - Yao, Song
AU - Till, Cathee
AU - Goodman, Phyllis J.
AU - Tangen, Catherine M.
AU - Wu, Yue
AU - Kristal, Alan R.
AU - Platz, Elizabeth A.
AU - Neuhouser, Marian L.
AU - Stanczyk, Frank Z.
AU - Reichardt, Juergen K.V.
AU - Santella, Regina M.
AU - Hsing, Ann
AU - Hoque, Ashraful
AU - Lippman, Scott M.
AU - Thompson, Ian M.
AU - Ambrosone, Christine B.
N1 - Funding Information:
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, 5Department 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: +1 716 845 8247; Fax: +1 716 845 8487; Email: li.tang@roswellpark.org
PY - 2011/10
Y1 - 2011/10
N2 - 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 = 1.70, 95% CI = 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 (<7 repeats)/long (≥7 repeats) genotype was significantly associated with the risk of low-grade prostate cancer (OR = 1.34, 95% CI = 1.05-1.70) compared with the short/short genotype. No significant association was found with CYP11A1. These associations were not observed among men in the finasteride arm. The results indicate that repeat polymorphisms in genes involved in estrogen biosynthesis and metabolism may influence risk of prostate cancer but that their effects may be modified by factors altering hormone metabolism, such as finasteride treatment.
AB - 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 = 1.70, 95% CI = 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 (<7 repeats)/long (≥7 repeats) genotype was significantly associated with the risk of low-grade prostate cancer (OR = 1.34, 95% CI = 1.05-1.70) compared with the short/short genotype. No significant association was found with CYP11A1. These associations were not observed among men in the finasteride arm. The results indicate that repeat polymorphisms in genes involved in estrogen biosynthesis and metabolism may influence risk of prostate cancer but that their effects may be modified by factors altering hormone metabolism, such as finasteride treatment.
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U2 - 10.1093/carcin/bgr139
DO - 10.1093/carcin/bgr139
M3 - Article
C2 - 21771722
AN - SCOPUS:80053153629
VL - 32
SP - 1500
EP - 1506
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 10
ER -