Abstract PR11: Exome sequencing identifies germline mutations in African American families with hereditary prostate cancer

Abstract

Abstract Prostate cancer (PCa) is the most common malignancy and the second leading cause of cancer death among men in the United States. Although it has been demonstrated that genetics plays a strong role in PCa, the genetic risk factors responsible for PCa remain poorly understood. Family history is a significant risk factor for PCa and African American (AA) men have the highest PCa incidence among ethnic/racial groups. Genetic analysis of AA families with PCa could facilitate the identification of genetic components contributing to PCa susceptibility. However, this area of research has not been sufficiently explored. We performed Exome sequencing on one affected and one unaffected man from one AA hereditary PCa family, which consists of 9 affected and 18 unaffected men in three generations. We identified 226 novel nonsynonymous variants in the affected man. We examined these mutations in remaining family members and narrowed down to 12 novel mutations which cosegregate with the disease in this family. Further analysis of the 12 mutations in affected and unaffected men from an additional 19 AA hereditary PCa families, 95 AA men with sporadic PCa and 95 unaffected AA control subjects identified three candidate gene mutations. One of the mutations was detected in three and the other two in two AA PCa families but they were either absent or were present in a very low frequency in unaffected control subjects. The three candidate mutations are now under further investigation in additional AA PCa families. The detailed bioinformatics analysis and the significance of these mutations in PCa susceptibility will be discussed. This abstract is also presented as Poster C67. Citation Format: Zemin Wang, Chiping Qian, Elisa M. Eledet, George Washington, Jovanny Zabaleta, Jennifer J. Hu, Diptasri Mandal, Wanguo Liu. Exome sequencing identifies germline mutations in African American families with hereditary prostate cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PR11. doi:10.1158/1538-7755.DISP13-PR11