• Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, U.S.A.
• O'Neal Comprehensive Cancer Center, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, U.S.A.
• Division of Intramural Research, National Institute on Minority Health and Health Disparities, Bethesda, MD, U.S.A.

Self-identified race and ethnicity (SIRE) and genetic ancestry (GA) are potentially associated with disparities in health outcomes; however, independent effects of SIRE and GA on mortality in cancer survivors including when adjusting for multiple risk factors are understudied. Among 23,445 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Screening Trial, SIRE was associated with mortality among prostate, colorectal, lung, ovarian, and breast cancer survivors; GA was associated with mortality among prostate, colorectal, and breast cancer survivors. Associations were strong when adjusting for age at cancer diagnosis, sex, and tumor characteristics, but attenuated when adjusting for individual-level factors and population-level socioeconomic status. For example, mortality risk was higher among Black vs White prostate cancer survivors and African GA vs European GA, but associations were attenuated after multilevel adjustment. Results suggest SIRE and GA do not solely reflect biologic variation; rather, social factors may drive mortality differences by SIRE and GA.