Estrogen receptors alpha (rs2234693 and rs9340799), and beta (rs4986938 and rs1256049) genes polymorphism in prostate cancer: Evidence for association with risk and histopathological tumor characteristics in Iranian men

We evaluated the effect of estrogen receptor (ER)-a and ER-beta genes polymorphisms on development of prostate cancer (PCa) and its correlation with serum reproductive hormones and with clinicopathological characteristics in a sample of Iranian men. One hundred sixty-two men with PCa (mean age 63.7+/-13.4 years) and 324 age-matched healthy controls (mean age 63.1+/-13.2 years) were recruited in this study. Genotypes for ER-a and ER-beta genes polymorphisms were identified by the polymerase chain reactionrestriction fragment length polymorphism (PCRRFLP) analysis. Serum levels of reproductive hormones were also measured. Of PCa patients, 38.3%, and 61.7% had localized and advanced tumor, and 45.7%, and 54.3%, had low grade and high-grade cancer, respectively. There was a significant difference in genotype frequency distribution of ER-a gene polymorphism (P?=?0.002), and ER-beta gene polymorphism (P?=?0.003) between cancer patients and controls. The ER-a Pvull C allele carriers (TC or CC) had a significantly increased risk of PCa compared with the TT homozygotes [odds ratio (OR) 3.12; 95% confidence interval (CI) 1.875.84, and OR?=?4.73, 95% CI:2.447.33, respectively]. It was also found that the ER-a XbaI AG (OR?=?4.36; 95% CI:2.476.68; P?=?0.001) and ER-beta AluI AG (OR?=?2.66, 95% CI:1.614.16; P?=?0.004) genotypes were significantly associated with increased risk of PCa. The ER-beta RsaI genotype was not associated with PCa. Baseline serum free E2 levels tended to be lower in men with PCa (0.35+/-0.04?pg/ml) compared to healthy men (0.48+/-0.05?pg/ml). Genotypes which confer susceptibility for developing PCa, accompanied with lowest serum levels of free E2. In the Iranian population, genetic polymorphisms of the ER-a and ER-beta genes may be involved in the etiology of PCa. (c) 2012 Wiley Periodicals, Inc.