Influence of CYP11A1 (TTTTA)n polymorphism on disease progression, serum androgens, prognosis and risk in men with prostate cancer

Abstract

CYP11A1 encodes for the enzyme cytochrome P450scc which catalyzes the first step in the biosynthesis of all steroid hormones by cleaving the side chain of cholesterol, converting it into pregnenolone. The influence of polymorphic variation in CYP11A1 has been poorly studied in prostate cancer, although several previous studies have determined that the CYP11A1 (TTTTA)n repeat is associated with risk and outcome in other diseases. To this end, this study aims to determine if the (TTTTA)n polymorphism in CYP11A1 is related to disease progression in men receiving androgen deprivation therapy (ADT), serum androgens, prognosis, and risk. A total of 290 patients with prostate cancer and 105 healthy controls were genotyped using fragment analyses. Genotypes were compared to overall survival from diagnosis, and the progression free survival of men receiving either intermittent or, continuous ADT. The (TTTTA)6/(TTTTA)6 genotype had smaller decrease in serum testosterone following a spike in androgen concentration commonly observed in men receiving intermittent ADT (P = 0.046), and carriers of an allele with eight (TTTTA)n repeats failed continuous ADT therapy earlier after reaching PSA nadir (P = 0.028). This pilot study suggests that carriers of longer CYP11A1 (TTTTA)n repeats may have altered testosterone disposition, and poorer response to continuous ADT, but this polymorphism is not related to prognosis or risk.