Association between estrogen and androgen receptor genes and prostate cancer risk

Objective: Prostate cancer (PC) is one of the principal causes of death among men. Steroid hormones are involved in normal prostate growth and carcinogenesis. The purpose of our study was to investigate the effects on PC risk of polymorphisms from three steroid hormone receptor genes: the androgen (AR), and the alpha (ESR1) and beta (ESR2) estrogen receptors. Design and methods: The study was performed on a Caucasian population of 1.045 PC patients and 814 controls. Using a logistic regression model, the different alleles and genotypes from those polymorphisms were analyzed according to case/control status, the tumor aggressiveness, and the age at onset. Results: A significant association between PC risk and the pooled 4/5, 5/6, and 6/6 genotypes of the GGGA repeat located in the first intron of ESR1 (odds ratio (OR)= 3.00. 95% Cl= 1.32-6.82, P=0.008) was observed. When we stratified the cases, this association was confined to patients with a Gleason score of 2-4 (OR=8.34, 95% Cl=2.91-23.91, P<0.0001) or late onset PC (OR=2.91, 95% Cl= 1.22-6.93, P=0.016). An association between a short ARCAG repeat(less than 17 repeats) wasalsoobserved among patients with late onset PC (OR=2.34, 95% Cl= 1.15-4.76, P=0.019). Conclusions: These findings suggest that the GGGA repeat from ESR1 and the CAG repeat from AR may be associated with risk of late onset PC.