Abstract 943: A comprehensive examination of breast cancer risk loci in African American women

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in 4 regions that better defined risk associations in African American women. In this study of breast cancer in African American women (3,016 cases, 2,745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) showed an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at p<0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25) we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at p<5×10-6) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants, with one variant at the PAX9 locus replicating in an independent sample (1,657 cases and 2,028 controls of African ancestry; rs17104923, p=0.057). Directional consistency of association observed for ∼65-70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry. Citation Format: Ye Feng, Gary K. Chen, Daniel O. Stram, Robert C. Millikan, Christine B. Ambrosone, Esther M. John, Leslie Bernstein, Wei Zheng, Andrew F. Olshan, Jennifer J. Hu, Regina G. Ziegler, Sarah Nyante, Elisa V. Bandera, Sue A. Ingles, Michael F. Press, Sandra L. Deming, Jorge L. Rodriguez-Gil, Julie R. Palmer, Olufunmilayo I. Olopade, Dezheng Huo, Clement A. Adebamowo, Temidayo Ogundiran, Alex Stram, Karen Park, Kristin A. Rand, Stephen J. Chanock, Loic Le Marchand, Laurence N. Kolonel, David V. Conti, Douglas Easton, Brian E. Henderson, Christopher A. Haiman. A comprehensive examination of breast cancer risk loci in African American women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 943. doi:10.1158/1538-7445.AM2014-943