title: Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial.
abstract: 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.
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. li.tang@roswellpark.org
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.forename: Cathee
authors.initials: C
authors.lastname: Till
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Goodman
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.forename: Alan R
authors.initials: AR
authors.lastname: Kristal
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Marian L
authors.initials: ML
authors.lastname: Neuhouser
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Juergen K V
authors.initials: JK
authors.lastname: Reichardt
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.forename: Ann
authors.initials: A
authors.lastname: Hsing
authors.forename: Ashraful
authors.initials: A
authors.lastname: Hoque
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
mesh_terms: D001141:Aromatase / Q000235:genetics*; D016022:Case-Control Studies; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000494:pharmacology*; D004970:Estrone / Q000097:blood; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D011863:Radioimmunoassay; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012307:Risk Factors; D013739:Testosterone / Q000097:blood; D000099148:UGT1A1 Enzyme
chemical_list: D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D004247:DNA; D004958:Estradiol; D004967:Estrogens; D004970:Estrone; D014453:Glucuronosyltransferase; D013739:Testosterone; D000099148:UGT1A1 Enzyme; C561410:CYP19A1 protein, human