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PUBLICATION: Admixture mapping of African-American women in the AMBER Consortium identifies new loci for breast cancer and estrogen-receptor subtypes. Frontiers in Genetics. 2016 Sept 21 doi: 10.3389/fgene.2016.00170

by Ruiz-Narvaez EA, Sucheston-Campbell L, Bensen JT, Yao S, Haddad S, Haiman CA, Bandera EV, John EM, Bernstein L, Hu JJ, Ziegler RG, Deming SL, Olshan, AF, Ambrosone CB, Palmer JR, Lunetta KL.
Wed, Sep 21st 2016 04:00 pm

 ABSTRACT: Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER) breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative, and 601 triple-negative) and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population.

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