A comprehensive examination of breast cancer risk loci in African American women.

Abstract

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 ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have 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. 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.

• Authors: Ye Feng, Daniel O Stram, Suhn Kyong Rhie, 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, Gary K Chen, 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
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 23 Issue 20 Pg. 5518-26 (Oct 15 2014) ISSN: 1460-2083 [Electronic] England
• PMID: 24852375 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Receptors, Estrogen

Topics

• Black or African American (genetics)
• Breast Neoplasms (genetics)
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genetic Variation
• Genome-Wide Association Study
• Humans
• Polymorphism, Single Nucleotide
• Receptors, Estrogen (genetics)