Abstract C32: Native American genetic ancestry is protective against prostate cancer in African Americans and European Americans

Abstract

Abstract Prostate cancer (PCa) incidence and mortality varies by racial/ethnic groups in the U.S. African American (AA) men have a 60% higher incidence and twice the mortality rate of European America (EA) men, while Hispanic Americans and Native Americans have lower incidence rates than EA men. Several genetic admixture studies have examined the role of west African ancestry on prostate cancer risk in AA men, however the influence of Native American ancestry on PCa risk has not been explored. Here we evaluated the relationship between individual genetic ancestry proportions and the likelihood of PCa diagnosis and aggressiveness. Methods: We recruited 40-79 year old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for genotyping of 105 ancestry informative markers. West African, European, and Native American genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the likelihood of having high-risk PCa relative to controls, adjusting for age and family history of PCa. Results: In AAs, NAA ranged from 0.4% to 28.8%. Mean NAA was 4.6% in AA cases, while controls had mean NAA of 6.6%. NAA ranged from 0.5% to 17.4% in EAs. Mean NAA was 5.1% in cases and 6.8% in controls. NAA was negatively associated with PCa diagnosis. AA men in the highest quartile of NAA had significantly reduced odds of PCa diagnosis compared to men in the lowest quartile of NAA (OR 0.47, 95% C.I.: 0.29-0.77). Similarly, EA men in the highest quartile of NAA had significantly reduced odds of PCa diagnosis compared men in the lowest NAA quartile (OR 0.36, 95% C.I.: 0.21-0.61). Additional adjustment of body mass index, education, smoking, alcohol use, and marital status did not change the results. NAA was also negatively associated with diagnosis of high risk PCa in EAs (P=0.04) and also trending in the same direction in AAs however not significant. Conclusions: Our study reveals that NAA is protective against PCa diagnosis and high-risk PCa. Hispanic Americans and Native Americans have lower PCa incidence rates than AAs and EAs, and the identification of inherited genetic or environmental factors that are associated with high NAA may improve PCa risk prediction and/or help to develop prevention strategies. Citation Format: Adam Murphy, Ken Batai, Ebony Shah, Rick A. Kittles. Native American genetic ancestry is protective against prostate cancer in African Americans and European Americans. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C32.