Cumulative Effect Assessment of Common Genetic Variants on Prostate Cancer: Preliminary Studies.

ABSTRACT

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people. Genome Wide Association studies (GWASs) have generated multiple genetic variants associated with prostate cancer (PC) risk. Taking into account previously identified genetic susceptibility variants, the purpose of our study was to determine the cumulative association between four common SNPs and the overall PC risk. A total of 78 specimens from both PC and benign prostate hyperplasia (BPH) patients were included in the study. Genotyping of all selected SNPs was performed using the TaqMan assay. The association between each SNP and the PC risk was assessed individually and collectively. Analysis of the association between individual SNPs and PC risk revealed that only the rs4054823 polymorphism was significantly associated with PC, and not with BPH (p < 0.001). Statistical analysis also showed that the heterozygous genotype of the rs2735839 polymorphism is more common within the BPH group than in the PC group (p = 0.042). The cumulative effect of high-risk alleles on PC was analyzed using a logistic regression model. As a result, the carriers of at least one risk allele copy in each particular region had a cumulative odd ratio (OR) of 1.42 times, compared to subjects who did not have any of these factors. In addition, the combination of these four genetic variants increased the overall risk of PC by 52%. Our study provides further evidence of the cumulative effects of genetic risk factors on overall PC risk. These results should encourage future research to explain the interactions between known susceptibility variants and their contribution to the development and progression of PC disease.