AbstractEstrogen receptor (ER) α polymorphisms have been shown to be involved in the oncogenesis of several organs. We hypothesize that polymorphisms of the ERα gene are risk factors for prostate cancer. The genotypic distributions of six different loci (codons: 10 T → C, 87 G → C, 243 C → T, 325 C → G, 594 G → A, and intron 1 C → T) of the ERα gene were analyzed in prostate cancer tissues. The DNA from 115 cases of prostate cancer (Japanese population) was analyzed by sequence‐specific polymerase chain reaction (PCR) and direct sequencing to determine the genotypic and allelic frequencies of the six different polymorphic loci of ERα. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. Results of this study showed that the frequency of the variant genotype (C/C) on codon 10 was significantly higher in prostate cancer patients. The odds ratio (OR) was calculated as 3.26 compared to wild‐type (T/T) with a 95% confidence interval (CI) of 1.58–6.73. Allele frequency at codon 10 also differed between groups. No association was found between codon 10 polymorphism and the stage of cancer. Polymorphism was not observed in codon 87, and frequencies of genotypes and alleles at other loci (intron 1, codons 243, 325, and 594) were not statistically different between cancer and controls. The present study suggests that polymorphism in codon 10 of ERα may be a risk factor for prostate cancer. These results are important in understanding the role of ERα polymorphism in the pathogenesis of prostate cancer. © 2003 Wiley‐Liss, Inc.