Abstract B063: Association of genetic ancestry with all-cause mortality and cancer mortality among Black and White individuals in the PLCO cohort

Abstract

Abstract Introduction: It is unknown how much of the increased all-cause mortality and cancer mortality risk in Black individuals is due to race as a social construct versus biological factors such as genetic ancestry. We examined the association of genetic ancestry with all-cause mortality and cancer mortality, controlling for risk factors and self-reported race/ethnicity, in the PLCO cohort. Methods: We used PLCO data from 154,887 participants, including 7,708 Black individuals and 137,562 White individuals. Genetic ancestry was determined by GRAF (https://github.com/ncbi/graf) on a set of 10,000 pre-selected fingerprinting variants. Percent ancestry for each of Europe, Africa, and East-Asia was determined for each person. We fit Cox models for time to death or time to cancer death, controlling for smoking history and other risk factors. Results: Self-reported Black individuals had increased all-cause mortality (HR=1.27, 95%CI: 1.19-1.35, p<0.0001) and cancer mortality (HR=1.25 95%CI: 1.12-1.40, p<0.0001) versus self-reported White individuals. For White individuals, increases in European ancestry were associated with increased death risk, (HR=1.01 per 1% increase in European ancestry, 95% CI:1.01-1.02, p=0.0003) and cancer mortality (HR=1.01, 95%CI:1.00-1.02, p=0.02). For Black individuals, increases in African ancestry were also associated with increased death risk, (HR=1.01 per 1% increase in African ancestry, 95%CI: 1.00-1.01, p=0.01) and cancer mortality (HR=1.01, 95%CI: 1.00-1.04, p=0.13), although not statistically significant. Conclusions: For self-reported White individuals, increasing European ancestry was associated with an increased all-cause mortality and cancer mortality risk. For self-reported Black individuals, there was evidence that increasing African ancestry increases all-cause mortality risk, but not cancer mortality. However, associations with ancestry were small and may be vulnerable to residual confounding. Impact/Significance: A mechanistic explanation for this finding is unclear, but it could be related to population genetic “fitness” with reduced genetic admixture leading to decreased fitness for survival. Citation Format: Courtney D. Dill, Dontray Crump, Rebecca Landy, Li Cheung, Wen-Yi Huang, Sonja Berndt, Neal Freedman, Hormuzd Katki. Association of genetic ancestry with all-cause mortality and cancer mortality among Black and White individuals in the PLCO cohort [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B063.