Identification of Prostate Cancer Susceptibility Loci by Meta-analysis of Multi-ethnic GWAS and Predicting Prostate Cancer Risk with Polygenic Risk Scores
Principal Investigator: Dr Lindsay Sausville (Gordon)
Approved Research ID: 29148
Approval date: October 1st 2018
Prostate cancer (PrCa) has high genetic susceptibility. Despite the success of GWAS in identifying PrCa susceptibility loci, much of the genetic susceptibility to PrCa is still unexplained in European-descent populations, and susceptibility in diverse populations is even more poorly understood. Here we propose to evaluate the association of genetic variants with PrCa in men from the UK Biobank. These results will be combined with prior results from other PrCa studies in European-descent populations to potentially identify new PrCa susceptibility loci. Moreover, the UK Biobank summary results will be analyzed jointly with studies containing diverse populations to detect PrCa risk loci important in these groups. Broadly, the above analyses will allow for better understanding of genetic susceptibility to prostate cancer, while also addressing potential commonalities and differences in PrCa genetic risk among different ethnicities. While genetics strongly impact PrCa susceptibility, family history (FH) of disease does not accurately predict which men will develop disease, indicating FH is a poor indicator of genetic risk. Here we will use known PrCa loci to derive a cumulative measure of genetic risk known as a polygenic risk score (PRS), and we will investigate whether PRS identifies men with high genetic risk of PrCa. Identification of such men may potentially inform clinical decisions such as increasing the frequency of prostate-specific antigen (PSA) screening. These analyses will take approximately 12 months to complete.