Genetic impact on prostate anatomical variability during ageing: role of CYP17, SRD5A2 and androgen receptor genes polymorphisms.

Abstract

To investigate the role of genetic determinism on individual variability in age-related prostate changes, as defining 'normal' anatomy in prostate gland ageing is a challenge because the variability of changes in prostate morphology increases with age. We assessed the influence of androgen- and oestrogen-regulating genetic polymorphisms on age-related weight and stromal-ratio changes in the prostate, using an anatomical, autopsy-based study. We quantified weight and glandular/stromal ratio in 85 autopsy prostates from men aged > 50 years. We genotyped allelic variants of androgen-regulating genes [androgen receptor (CAG repeats) and type II 5-alpha reductase (TA repeat and V89L)] and an oestrogen-regulating gene (A1/A2 variants of the 17alpha-hydroxylase (CYP17)). There was a fair negative correlation between prostate weight and the number of CAG repeats (r = -0.32, P = 0.003); the group with < or = 19 CAG repeats had heavier prostates than the > or = 20 group (P = 0.015). The stromal ratio was higher in the group with 20-23 CAG repeats (P = 0.02) and in the A2A2 group of the CYP17 polymorphism (P = 0.016) compared with the other groups mixed together. A low number of CAG repeats is associated with higher prostate weights. The A2A2 genotype of CYP17 is associated with a higher stromal ratio.