Year: 2017
Type: article
Study design: Observational Study
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: 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
Institutions: University of Southern California, USC Norris Comprehensive Cancer Center, University of Chicago, Boston University, Roswell Park Comprehensive Cancer Center, Cancer Prevention Institute of California, Stanford Medicine, Stanford Cancer Institute, Stanford University, City Of Hope National Medical Center, City of Hope, Beckman Research Institute, Vanderbilt University, Vanderbilt-Ingram Cancer Center, University of Miami, University of Miami Health System, Sylvester Comprehensive Cancer Center, National Cancer Institute, Division of Cancer Epidemiology and Genetics, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Rutgers Cancer Institute, University of Ibadan, Harvard University, Dana-Farber Cancer Institute, University of Maryland, Baltimore, University of the West Indies, Stony Brook University, National Institutes of Health, University of Pennsylvania, University of Hawaii Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1017297203, G1161922357, Southern Community Cohort Study, G1272756610, Uncoupling obesity from breast cancer in African American women, G1492281636, G1569999668, G1660206989, A GENOME-WIDE BREAST CANCER SCAN IN AFRICAN AMERICANS, G2069482854, G2313542652, G2344417776, G2407663899, G2419028985, G275963511, G295662594, G299563851, Genome-wide association study of breast cancer in the African Diaspora, G3102336106, Breast Cancer Family Registry, G3465312822, Breast Cancer Risk Enhancers, G3708204173, G4119534169, G429713427, G4356264197, G4450071017, G4513176822, G4592503987, G4858979163, G4907478063, G5305488713, The Nashville Breast Health Study, G5446091787, G5528430224, G5624755341, G5654214539, G5824370075, G5850682332, G5853943267, G7011691652, G725763919, Epidemiology of Breast Cancer Subtypes in African American Women: a Consortium, A Follow-up Study for Causes of Cancer in Black Women, Integrated Training For Physician-Scientists, SPORE in Breast Cancer, G7646998162, G7697152668, G7740288598, G8056846548, G8389391685, G8820111440, G884543044, G8880508232, G9000007592, G9000021152, G9000043966, G9000051068, G9000061634, G9000062283, G9000073604, G9000081609, G9000083102, G9000084571, G9000118332, G9000147011, G9000173417, G9000176900, G9000179242, G9000179783, G9000180252, G9000182874, G9000192259, G9000207854, G9000216949, G9000233422, G9000266857, G9000355445, UNC Center for Environmental Health and Susceptibility, Cancer Center Support Grant, G908924418
OpenAlex ID: W2604601654