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A Comprehensive Examination of Breast Cancer Risk Loci in African American Women

Citation

Feng, Ye; Stram, Daniel O.; Rhie, Suhn K.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F.; & Hu, Jennifer J., et al. (2014). A Comprehensive Examination of Breast Cancer Risk Loci in African American Women. Human Molecular Genetics, 23(20), 5518-5526. PMCID: PMC4168823

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 x 10-6) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for approximately 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.

URL

http://dx.doi.org/10.1093/hmg/ddu252

Reference Type

Journal Article

Year Published

2014

Journal Title

Human Molecular Genetics

Author(s)

Feng, Ye
Stram, Daniel O.
Rhie, Suhn K.
Millikan, Robert C.
Ambrosone, Christine B.
John, Esther M.
Bernstein, Leslie
Zheng, Wei
Olshan, Andrew F.
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah J.
Bandera, Elisa V.
Ingles, Sue Ann
Press, Michael F.
Deming, Sandra L.
Rodriguez-Gil, Jorge L.
Palmer, Julie R.
Olopade, Olufunmilayo I.
Huo, Dezheng
Adebamowo, Clement A.
Ogundiran, Temidayo O.
Chen, Gary K.
Stram, Alexander
Park, Karen
Rand, Kristin A.
Chanock, Stephen J.
Le Marchand, Loic
Kolonel, Laurence N.
Conti, David V.
Easton, Douglas F.
Henderson, Brian E.
Haiman, Christopher A.

PMCID

PMC4168823