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Genetic polymorphisms of estrogen receptor alpha, CYP19 , catechol‐ O ‐methyltransferase are associated with familial prostate carcinoma risk in a Japanese population
Author(s) -
Suzuki Kazuhiro,
Nakazato Haruki,
Matsui Hiroshi,
Koike Hidekazu,
Okugi Hironobu,
Kashiwagi Bunzo,
Nishii Masahiro,
Ohtake Nobuaki,
Nakata Seiji,
Ito Kazuto,
Yamanaka Hidetoshi
Publication year - 2003
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.11639
Subject(s) - prostate cancer , medicine , genotype , odds ratio , catechol o methyl transferase , estrogen receptor , prostate , oncology , estrogen , endocrinology , allele , breast cancer , cancer , biology , genetics , gene
Abstract BACKGROUND Estrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen‐related enzymes and receptors and the risk of developing familial prostate carcinoma. METHODS In the current study, 101 cases with prostate carcinoma whose first‐degree relatives had prostate carcinoma and 114 healthy age and residence‐matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase ( CYP19 ), and catechol‐ O ‐methyltransferase ( COMT ) genes were analyzed. RESULTS For single polymorphisms, a significant association of the T/T genotype of the Pvu II site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97–5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02–3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85–2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high‐grade carcinoma (OR, 2.59; 95% CI, 1.47–4.46; P = 0.048). The number of high‐risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19 , and the G/A in COMT ) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72–5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61–10.99; P = 0.002). CONCLUSIONS Genetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low‐penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma. Cancer 2003;98:1411–6. © 2003 American Cancer Society. DOI 10.1002/cncr.11639