Genetic Variations in Androgen Metabolism Genes and Associations with Prostate Cancer in South African Men (Original Articles) (Report‪)‬

Prostate cancer (PCa) is the second most common histologically diagnosed malignancy in South African men, with an estimated annual incidence rate of 17.8/100 000.1 The age-standardised incidence rate (ASIR) of PCa in South African men in the 55 59-year age range is 56/100 000; this figure rises to 455/100 000 in men older than 75 years. (1) In North America, incidences of PCa are the highest in black men, intermediate in white men and the lowest in Asian men. (2) In South Africa, the highest incidence is reported in white men (Northern European ancestry) and the lowest in black and Asian men, with an intermediate incidence reported for coloured (mixed ancestry) men. (1) However, substantial under-diagnosis and under-reporting may be the reason for the low incidence in South African black men. (3) It has been suggested that ethnic differences in incidence and mortality of PCa are related to genetic variations in genes that regulate androgen metabolism. Studies addressing this hypothesis have demonstrated that genes that regulate androgen metabolism are associated with PCa susceptibility. Findings include genes that encode proteins belonging to the cytochrome P450 (CYP) family (a group of enzymes that are involved in the metabolism of xenobiotics, steroids, vitamins and sex hormones). (4) The CYP3A subfamily is a group of enzymes that are key deactivators of testosterone. The CYP3A locus consists of four genes, CYP3A5, CYP3A7, CYP3A4 and CYP3A43, each gene containing 13 exons and located on chromosome 7q2122.1. We did not screen CYP3A7 because it is predominantly expressed in fetal stages of development (4) and we therefore considered it unlikely to play a role in the pathogenesis of PCa.