Genetic Variation in Cancer Risk and Outcomes in African Americans

Project Summary/Abstract—Overall Program Genetic testing for both germline and somatic mutations has improved our understanding of the basic biology of carcinogenesis, identified high-risk populations for targeted prevention and screening, identified targets for new treatment strategies, and has led to some of the most significant inroads in reducing cancer burden. Yet, there

is still much to learn about the role of inherited genetic susceptibility and cancer, and the significant barriers to accessing genetic counseling and testing services, particularly in under-represented populations. We have assembled one of the largest populations of African American cancer survivors to date to study genetic

susceptibility in this population. The Detroit Research on Cancer Survivors (ROCS) (U01CA199240) cohort includes participants considered to be at particularly high-risk due to family history of cancer, age at diagnosis or a diagnosis of a second primary cancer, and the infrastructure will be used to expand participation. The

Program includes three projects and two cores with an overall goal of improving the identification and clinical management of hereditary and multiple primary cancers in African Americans, who are currently underrepresented in genetic research. To do this we will: 1) Use bioinformatic analyses, family structure, gene

expression, and somatic alterations to identify African American cancer survivors most likely to harbor high- penetrance genetic variants currently classified as pathogenic or having uncertain significance; 2) Characterize the spectrum of germline genetic variation in African Americans with multiple primary cancers in relation to known

pathogenic mutations, site-specific polygenic risk scores (PRS), and largely modifiable non-genetic risk factors; and 3) Develop an online, culturally adapted educational intervention to increase access to genetic counseling information among medically underserved African Americans and uptake of risk-appropriate genetic testing

among those at increased risk so that we are poised to translate novel genetic discoveries into clinical practice.