title: Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.
abstract: Background:Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry.Methods:We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT).Results:Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P< 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality.Conclusions:Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry.Impact:The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry.Cancer Epidemiol Biomarkers Prev; 26(7); 1016-26. ©2017 AACR.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California. haiman@usc.edu yefeng@usc.edu.
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authors.lastname: Feng
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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authors.initials: SK
authors.lastname: Rhie
authors.affiliation: Department of Public Health Sciences, University of Chicago, Chicago, Illinois.
authors.forename: Dezheng
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authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
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authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
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authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Christine B
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authors.affiliation: Cancer Prevention Institute of California, Fremont, California.|Department of Health Research and Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
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authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California.
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authors.lastname: Bernstein
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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authors.affiliation: Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Jennifer J
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authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
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authors.lastname: Ziegler
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
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authors.lastname: Nyante
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
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authors.lastname: Bandera
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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authors.lastname: Ingles
authors.affiliation: Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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authors.affiliation: Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida.
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authors.initials: JL
authors.lastname: Rodriguez-Gil
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
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authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York.
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authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
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authors.initials: TO
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authors.affiliation: Dana Farber Cancer Institute & Harvard T. H. Chan School of Public Health, Boston, Maryland.
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authors.lastname: Rebbeck
authors.affiliation: Department of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, Maryland.
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authors.lastname: Adebamowo
authors.affiliation: Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
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authors.affiliation: Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.
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authors.affiliation: Chronic Disease Research Centre, Tropical Medicine Research Institute, University of the West Indies, Bridgetown, Barbados.|Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, New York.
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authors.affiliation: Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, New York.
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authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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authors.initials: KL
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authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
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authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
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authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
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authors.initials: AF
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authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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authors.initials: DV
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authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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authors.initials: GA
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authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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authors.initials: DO
authors.lastname: Stram
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
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authors.initials: OI
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authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
authors.forename: Julie R
authors.initials: JR
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authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California. haiman@usc.edu yefeng@usc.edu.
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authors.initials: CA
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mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen