Genetic Predictors of Prostate Cancer Survival

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Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-21-049. Even though most men diagnosed with prostate cancer will not die of the disease, prostate cancer is still the second leading cause of cancer death among men in the United States. While screening for prostate cancer reduces death from disease, this comes at the price of both unnecessary biopsies that reveal no evidence of cancer and treatment of otherwise indolent cancer resulting in unnecessary adverse events. Therefore, there is an unmet need for improved screening tools for prostate cancer. This need is especially important in the African-American population, as African-American men are both more likely to be diagnosed with prostate cancer and to die from the disease if diagnosed. However, to date, most genetic studies on prostate cancer have been conducted in individuals of European ancestry. To address this need, we are conducting an NCI-funded study, “Genetic Predictors of Prostate Cancer Survival”, whose goal is to identify genetic variants associated with survival time in men with prostate cancer. This will be achieved both by testing both imputed gene expression levels, derived from common variants, and pathogenic changes in coding genes, derived from rare coding variants, with survival. In the initial grant, we proposed to validate our findings using several cohorts, including a series of 300 radical prostatectomy patients from African-American patients from the Durham VA hospital we have collected. Here, we are proposing to double the sample size by retrieving samples and extracting clinical annotation for an additional 300 African-American men from this cohort. These samples will then be genotyped using the resources of CIDR. With their deposition in dbGaP, this genetic data will both increase the power and diversity of our studies of the genetics of prostate cancer survival and be of use to others studying genomic influences on disease in African-Americans, both for their data on prostate cancer and as a reference panel for other studies.