Androgen Pathway Related Gene Variants and Prostate Cancer Association in Auckland Men

Multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer (PC) have been reported in statistically robust studies in the past but these require an in-depth mechanistic understanding with respect to the biological pathways leading to disease. The current study was carried out to examine the PC and benign urology disease risk associations with lifestyle, demographic and genetic factors in a group of men between the ages 40-81 years from Auckland, New Zealand. The data presented herein support a significant positive association of PC risk with tobacco smoking, and a negative association with alcohol intake. The BMI was not associated with disease risk. The SRD5A2 rs632148 G allele was associated with PC compared to those with benign urology disease, after adjustments were made for the confounding variables. The Gleason score as well as disease aggressiveness of the PC group showed no association with lifestyle, demographic factors or the SNPs studied. The levels of prostate-specific antigen (PSA) significantly increased with age, smoking status and BMI, and decreased with alcohol consumption. The AKR1C3 rs12529 G allele was significantly associated with lower PSA levels in PC and benign urology disease groups compared to healthy controls. The G allele of the SRD5A2 rs632148 SNP has shown a significant interaction with PSA and a higher Gleason score outcome. Taken together, these findings show the utility of these gene variants and patient lifestyle history, together with the diagnostic serum PSA levels, to collectively enhance the understanding of the clinical-pathological variables of PC. Such information will support the selection of more personalised treatment options for this disease greatly impacting public health.