Abstract IA42: Genome wide association for breast cancer risk in Latinas: Analysis of known susceptibility loci

Abstract

Abstract Background: Genome wide association studies have identified over 90 common variants associated with breast cancer risk. The majority of these findings have been made in populations of European ancestry. We have performed a genome wide association study of in ~2400 US Latina and Mexican breast cancer cases and ~7500 controls. Here we report on examination of previously reported loci and fine mapping within those loci. Methods: Cases and controls included women from the San Francisco Bay Area Study, the Northern California Breast Cancer Family Registry, the Multi-Ethnic Cohort and the Kaiser Permanente Research Program on Genes and the Environment on Health all based in California. In addition we included cases and controls from the CAMA study, based in Mexico and recruiting from 4 different states: Mexico City, Veracruz, Monterrey, and Puebla. Each of the samples were genotyped using an array with genome wide coverage (Affymetrix 6.0, Affymetrix Axiom, Illumina 1M, Illumina 2.5M or Illumina Oncoarray). We inferred genetic ancestry using principal components analysis. We imputed each array to the Haplotype Reference Consortium and performed association testing with breast cancer using logistic regression models, adjusting for study, array used, and principal components 1-10. Results: We have identified several signals at 6q25 which are independent of previously reported SNPs in other populations. We have also evaluated the utility of polygenic risk using data from common variants at previously reported loci. We compared a range of algorithms to enhance the predictive power of polygenic risk in Latinas, including ones that utilize fine mapping vs. ones which use the top SNPs from other populations. Conclusion: We demonstrate that a combination of new variants and judicious use of data from the known loci generates useful polygenic risk for breast cancer in Latinas. Citation Format: Joshua Hoffman, Sarah Sawyer, Laura Fejerman, Donglei Hu, Scott Huntsman, Esther John, Gabriela Torres-Mejia, Larry Kushi, Chistopher Haiman, Elad Ziv. Genome wide association for breast cancer risk in Latinas: Analysis of known susceptibility loci. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA42.