Roswell Park Cancer Institute, Department of Cancer Prevention and Control, Buffalo, New York.
The etiology of prostate cancer remains elusive, although steroid hormones likely 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 vs. placebo as a chemoprevention agent. Using data and specimens from 1,154 cases and 1,351 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 to 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 to 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.
Tang L, Yao S, Till C, Goodman PJ, Tangen CM, Wu Y, Kristal AR, Platz EA, Neuhouser ML, Stanczyk FZ, Reichardt JK, Santella RM, Hsing A, Hoque A, Lippman SM, Thompson IM, Ambrosone CB. Are you the author?
Reference: Carcinogenesis. 2011 Jul 18. Epub ahead of print.