Admixture Mapping of African–American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes

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  • Ruiz-Narváez, Edward A.
    • Other Affiliation: Slone Epidemiology Center; Boston University
  • Sucheston-Campbell, Lara
    • Other Affiliation: College of Pharmacy; The Ohio State University
  • Bensen, Jeannette T.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Yao, Song
    • Other Affiliation: Department of Cancer Prevention and Control; Roswell Park Cancer Institute
  • Haddad, Stephen
    • Other Affiliation: Slone Epidemiology Center; Boston University
  • Haiman, Christopher A.
    • Other Affiliation: Department of Preventive Medicine; Keck School of Medicine; University of Southern California/Norris Comprehensive Cancer Center
  • Bandera, Elisa V.
    • Other Affiliation: Rutgers Cancer Institute of New Jersey
  • John, Esther M.
    • Other Affiliation: Cancer Prevention Institute of California
  • Bernstein, Leslie
    • Other Affiliation: Division of Cancer Etiology; Department of Population Science; Beckman Research Institute
  • Hu, Jennifer J.
    • Other Affiliation: Sylvester Comprehensive Cancer Center and Department of Public Health Sciences; University of Miami Miller School of Medicine
  • Ziegler, Regina G.
    • Other Affiliation: Epidemiology and Biostatistics Program; Division of Cancer Epidemiology and Genetics; National Cancer Institute
  • Deming, Sandra L.
    • Other Affiliation: Vanderbilt Epidemiology Center; Vanderbilt University and the Vanderbilt-Ingram Cancer Center
  • Olshan, Andrew F.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Ambrosone, Christine B.
    • Other Affiliation: Department of Cancer Prevention and Control; Roswell Park Cancer Institute
  • Palmer, Julie R.
    • Other Affiliation: Slone Epidemiology Center; Boston University
  • Lunetta, Kathryn L.
    • Other Affiliation: Department of Biostatistics; Boston University School of Public Health
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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  • Article
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  • In Copyright
Journal title
  • Frontiers in Genetics
Journal volume
  • 7
Language
  • English
ISSN
  • 1664-8021

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