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

Abstract

We evaluated the effect of estrogen receptor (ER)-α and ER-β 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 ± 3.4 years) and 324 age-matched healthy controls (mean age 63.1 ± 3.2 years) were recruited in this study. Genotypes for ER-α and ER-β genes polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) 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-α gene polymorphism (P = 0.002), and ER-β gene polymorphism (P = 0.003) between cancer patients and controls. The ER-α 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) 1.87-5.84, and OR = 4.73, 95% CI:2.44-7.33, respectively]. It was also found that the ER-α XbaI AG (OR = 4.36; 95% CI:2.47-6.68; P = 0.001) and ER-β AluI AG (OR = 2.66, 95% CI:1.61-4.16; P = 0.004) genotypes were significantly associated with increased risk of PCa. The ER-β 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-α and ER-β genes may be involved in the etiology of PCa.