Enhancing Global Diversity in Cancer Clinical Genetics

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PROJECT SUMMARY/ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 20-032. Inherited genetic information can reduce cancer risk and mortality using protocols for patient ascertainment, testing, counseling, prevention, and treatment. There is growing evidence that inherited genetic mutations represent a large proportion of cancer cases in sub-Saharan Africa (SSA). Nigerian breast cancer cases have a 2.5-fold higher rate of inherited susceptibility mutations than US Whites, with BRCA2 being the most commonly mutated in Nigerian breast cancer, and higher rates of BRCA and TP53 mutations compared to observations made in Caucasians in Rwanda. These preliminary observations highlight the need for further large studies to better define the inheritance of breast cancer risk in SSA. Most cancer genetic testing data does not represent the racial and ethnic diversity of the US or global population. This deficit of diverse populations in cancer genetics research limits the application of these data to all populations. In addition, it has been demonstrated that genetic misdiagnoses can arise when diverse populations and their mutational spectrum is not included when making inferences about pathogenicity and risk and can exacerbate health disparities. Thus, studies that include a broader spectrum of individuals in cancer genetics research will benefit all populations. In order to develop and evaluate the potential for genetic testing in SSA, we propose a proof of concept feasibility study of hereditary cancer that will contribute data on the prevalence of hereditary cancer mutations in SSA and inform the development of SSA-specific guidelines for cancer genetic testing. We will address these goals by undertaking the following specific aims: Specific Aim 1: Develop and evaluate a set of essential cancer genetic protocols for cancer genetic testing, counseling, and management in low resource settings; and Specific Aim 2: Undertake a pilot evaluation of research genetic testing and counseling in 100 breast and prostate cancer cases in Rwanda. The proposed pilot research will not only enhance cancer genetics research and clinical translation in SSA but will address the critical need for increased ethnic diversity in cancer genetics data, which to date has been dominated by European ancestry data. Ethnically diverse genetic data will aid in the appropriate development and implementation of cancer genetic testing for all populations, and in particular will reduce the potential for genetic misdiagnoses and improved interpretation of cancer genetic risk in US populations.