Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry

Ye Feng; Suhn Kyong Rhie; Dezheng Huo; Edward A Ruiz-Narvaez; Stephen A Haddad; Christine B Ambrosone; Esther M John; Leslie Bernstein; Wei Zheng; Jennifer J Hu; Regina G Ziegler; Sarah Nyante; Elisa V Bandera; Sue A Ingles; Michael F Press; Sandra L Deming; Jorge L Rodriguez-Gil; Yonglan Zheng; Song Yao; Yoo-Jeong Han; Temidayo O Ogundiran; Timothy R Rebbeck; Clement Adebamowo; Oladosu Ojengbede; Adeyinka G Falusi; Anselm Hennis; Barbara Nemesure; Stefan Ambs; William Blot; Qiuyin Cai; Lisa Signorello; Katherine L Nathanson; Kathryn L Lunetta; Lara E Sucheston-Campbell; Jeannette T Bensen; Stephen J Chanock; Loic Le Marchand; Andrew F Olshan; Laurence N Kolonel; David V Conti; Gerhard A Coetzee; Daniel O Stram; Olufunmilayo I Olopade; Julie R Palmer; Christopher A Haiman

doi:10.1158/1055-9965.EPI-16-0567

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Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry

Journal article

Open access

Peer reviewed

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry

Ye Feng, Suhn Kyong Rhie, Dezheng Huo, Edward A Ruiz-Narvaez, Stephen A Haddad, Christine B Ambrosone, Esther M John, Leslie Bernstein, Wei Zheng, Jennifer J Hu, …

Cancer epidemiology, biomarkers & prevention, Vol.26(7), pp.1016-1026

2017-07

DOI: https://doi.org/10.1158/1055-9965.EPI-16-0567

PMCID: PMC5500414

PMID: 28377418

Abstract

Genetic Predisposition to Disease

Receptors, Estrogen - metabolism

Humans

Risk Factors

African Americans - genetics

Chromosome Mapping

Genetic Loci

Case-Control Studies

Breast Neoplasms - genetics

Breast Neoplasms - pathology

Alleles

Female

Biomarkers, Tumor - genetics

Polymorphism, Single Nucleotide

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. 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). 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 ( < 0.05). Through fine-mapping, in six regions ( ), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions ( ), 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. Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry. The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. .

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.189 Genome Studies; 1.189.597 BRCA1
Web Of Science research areas: Oncology; Public, Environmental & Occupational Health
ESI research areas: Social Sciences, general

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Title: Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry
Creators: Ye Feng - 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
Suhn Kyong Rhie - Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Dezheng Huo - Department of Public Health Sciences, University of Chicago, Chicago, Illinois
Edward A Ruiz-Narvaez - Slone Epidemiology Center at Boston University, Boston, Massachusetts
Stephen A Haddad - Slone Epidemiology Center at Boston University, Boston, Massachusetts
Christine B Ambrosone - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York
Esther M John - Department of Health Research and Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California
Leslie Bernstein - Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California
Wei Zheng - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Jennifer J Hu - Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida
Regina G Ziegler - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
Sarah Nyante - Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
Elisa V Bandera - Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
Sue A Ingles - Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Michael F Press - Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Sandra L Deming - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Jorge L Rodriguez-Gil - Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida
Yonglan Zheng - Department of Medicine, University of Chicago, Chicago, Illinois
Song Yao - Roswell Park Cancer Institute, Buffalo, New York
Yoo-Jeong Han - Department of Medicine, University of Chicago, Chicago, Illinois
Temidayo O Ogundiran - Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria
Timothy R Rebbeck - Dana Farber Cancer Institute & Harvard T. H. Chan School of Public Health, Boston, Maryland
Clement Adebamowo - Department of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, Maryland
Oladosu Ojengbede - Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria
Adeyinka G Falusi - Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
Anselm Hennis - Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, New York
Barbara Nemesure - Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, New York
Stefan Ambs - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland
William Blot - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Qiuyin Cai - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Lisa Signorello - Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, Maryland
Katherine L Nathanson - Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Kathryn L Lunetta - Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
Lara E Sucheston-Campbell - Roswell Park Cancer Institute, Buffalo, New York
Jeannette T Bensen - Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
Stephen J Chanock - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
Loic Le Marchand - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
Andrew F Olshan - Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
Laurence N Kolonel - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
David V Conti - Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Gerhard A Coetzee - Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Daniel O Stram - Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Olufunmilayo I Olopade - Department of Medicine, University of Chicago, Chicago, Illinois
Julie R Palmer - Slone Epidemiology Center at Boston University, Boston, Massachusetts
Christopher A Haiman - 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
Publication Details: Cancer epidemiology, biomarkers & prevention, Vol.26(7), pp.1016-1026
Publisher: United States
Grant note: R01 CA063464 / NCI NIH HHS R01 CA098663 / NCI NIH HHS R01 CA185623 / NCI NIH HHS R01 CA054281 / NCI NIH HHS R01 CA092447 / NCI NIH HHS U01 CA182898 / NCI NIH HHS UM1 CA164920 / NCI NIH HHS T32 GM008692 / NIGMS NIH HHS P30 CA016086 / NCI NIH HHS R01 CA100374 / NCI NIH HHS UM1 CA164974 / NCI NIH HHS P50 CA058223 / NCI NIH HHS U01 CA179715 / NCI NIH HHS P01 CA151135 / NCI NIH HHS P30 CA068485 / NCI NIH HHS R01 CA142996 / NCI NIH HHS R01 CA058420 / NCI NIH HHS P50 CA125183 / NCI NIH HHS P30 ES010126 / NIEHS NIH HHS R01 CA190182 / NCI NIH HHS U01 CA164973 / NCI NIH HHS R01 CA073629 / NCI NIH HHS R01 CA100598 / NCI NIH HHS R01 CA089085 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Public Health Sciences Research
Language: English
Resource Type: Journal article
PMID: 28377418
PMCID: PMC5500414
Record Identifier: 991031559793702976