Genetic polymorphisms of hormone-related genes and prostate cancer risk in the Japanese population

Carcinogenesis of the prostate involves androgen influences, and associations between genetic polymorphisms of androgen receptor and metabolizing enzymes and prostate cancer risk have been reported. Roles for non-androgenic hormones are not well defined, but they also may have an impact judging from epidemiological and animal experimental alphalambda zetaof data. The purpose of the study was to determine whether hormone-related polymorphisms are associated with prostate cancer risk. A case-control study was performed with 147 Japanese prostate cancer patients and 266 urological controls. Polymorphisms of target genes [cytochrome P450 (CYP) 1B1, Leu(432) Val; debrisoquine hydroxylase, (CYP2D6)*4, aromatase (CYP19), Arg(264) Cys; estrogen receptor (ER)alpha-Xx (Xba I) and Pp (Pvu II); ERbeta-Rr (Rsa I); progesterone receptor (PR) Alu in intron 71 were examined by PCR-based methods. The capital and small letters signify the absence and presence of restriction sites, respectively. Odds ratios (OR) were adjusted for age using multiple logistic regression analysis with SPSS Medical Pack. Among the seven examined genetic polymorphisms, significant associations between CYP1B1 Leu(432)Val (OR 4.80; 95% confidence interval (CI), 1.21-19.05) and Alu in intron 7 of PR (OR 4.17; 95%CI, 1.26-13.85) were found. As for combined effects, the CYP1B1 polymorphisms (Leu/Val+Val/Val) together with heterozygosity for Alu in the PR were more frequent among prostate cancer patients (1.45%) than controls (0.41%), although without significance (OR, 3.99; 95%CI, 0.36-44.8). The combination of ERalpha (P/p+p/p) polymorphisms with heterozygosity for Alu in the PR demonstrated an OR of 4.56 (95%CI, 1.01-20.6). This pilot study showed that CYP1B1 and PR polymorphisms, alone or in combination, might be associated with prostate cancer risk. They might, therefore, have potential as a tool for identifying high-risk individuals.