Associations between estrogen receptor genetic polymorphisms, smoking status, and prostate cancer risk: a case–control study in Japanese men

Abstract

Objective: Prostate cancer (PCa) is one of the major causes of death among men. Our study investigated the association of ESR1 and ESR2 genotypes with susceptibility to PCa in relation to smoking status in Japanese. Method: A case–control study was performed with 750 Japanese prostate cancer patients and 870 healthy controls. After age-matching in case–controls, 352 controls and 352 cases were enrolled in this study. By using logistic regression analysis, the different genotypes from ESR1 and ESR2 were analyzed according to case/control status. Result: ESR2 rs4986938 AG and AG + AA genotypes were associated with significantly decreased risk of PCa (AG: OR = 0.68, 95 % CI 0.47–0.97, P < 0.05 and AG + AA: OR = 0.67, 95 % CI 0.47–0.94, P < 0.05). However, there was no significant association between ESR1 rs2234693 and PCa risk. When patients were grouped according to smoking status, the ESR2 rs1256049 AA genotype (OR = 0.48, 95 % CI 0.25–0.95, P < 0.05) and ESR2 rs4986938 AG + AA genotype (OR = 0.64, 95 % CI 0.41–1.00, P < 0.05) showed significantly decreased PCa risk in the ever-smoker group. Conclusion: Our results suggest that the estrogen receptor ESR2 has a very important function to predict PCa and that different SNPs have different predictive values. Smoking may influence estrogenic activity and may influence PCa together with the estrogen receptor.