TY - JOUR
T1 - Characterizing genetic susceptibility to breast cancer in women of african ancestry
AU - Feng, Ye
AU - Rhie, Suhn Kyong
AU - Huo, Dezheng
AU - Ruiz-Narvaez, Edward A.
AU - Haddad, Stephen A.
AU - Ambrosone, Christine B.
AU - John, Esther M.
AU - Bernstein, Leslie
AU - Zheng, Wei
AU - Hu, Jennifer J.
AU - Ziegler, Regina G.
AU - Nyante, Sarah
AU - Bandera, Elisa V.
AU - Ingles, Sue A.
AU - Press, Michael F.
AU - Deming, Sandra L.
AU - Rodriguez-Gil, Jorge L.
AU - Zheng, Yonglan
AU - Yao, Song
AU - Han, Yoo Jeong
AU - Ogundiran, Temidayo O.
AU - Rebbeck, Timothy R.
AU - Adebamowo, Clement
AU - Ojengbede, Oladosu
AU - Falusi, Adeyinka G.
AU - Hennis, Anselm
AU - Nemesure, Barbara
AU - Ambs, Stefan
AU - Blot, William
AU - Cai, Qiuyin
AU - Signorello, Lisa
AU - Nathanson, Katherine L.
AU - Lunetta, Kathryn L.
AU - Sucheston-Campbell, Lara E.
AU - Bensen, Jeannette T.
AU - Chanock, Stephen J.
AU - Le Marchand, Loic
AU - Olshan, Andrew F.
AU - Kolonel, Laurence N.
AU - Conti, David V.
AU - Coetzee, Gerhard A.
AU - Stram, Daniel O.
AU - Olopade, Olufunmilayo I.
AU - Palmer, Julie R.
AU - Haiman, Christopher A.
N1 - Funding Information:
Acknowledgments This research was funded by the NIH and Foundation grants: P01 CA151135, R01 CA058420, UM1 CA164974, R01 CA098663, R01 CA100598, R01 CA185623, UM1 CA164973, R01 CA54281, R01 CA063464, R01 CA190182, P50 CA58223, U01 CA179715, R01 CA142996, P50 CA125183, and R01 CA89085, the Department of Defense Breast Cancer Research Program, Era of Hope Scholar Award Program W81XWH-08-1-0383 (AABC); the Susan G. Komen for the Cure Foundation; the Breast Cancer Research Foundation; and the University Cancer Research Fund of North Carolina. Pathology data were obtained from numerous state cancer registries (Arizona, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Georgia, Hawaii, Illinois, Indiana, Kentucky, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, North Carolina, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia). Studies in AABC were supported by National Institute for Child Health and Development contract NO1-HD-3-3175 (CARE), NIH grant CA100374, and the Biospecimen Core Lab that is supported in part by the Vanderbilt-Ingram Cancer Center (CA68485; NBHS), by NIH grant CA73629 (WFBC), NIH grant CA77305 and United States Army Medical Research Program grant DAMD17-96-6071 (SFBCS), by NIH grant CA164920 (NC-BCFR). The Breast Cancer Family Registry (BCFR) was supported by grant UM1 CA164920 from the U.S. National Cancer Institute. Genotyping of the PLCO samples was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH.
Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85022324039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85022324039&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-16-0567
DO - 10.1158/1055-9965.EPI-16-0567
M3 - Article
C2 - 28377418
AN - SCOPUS:85022324039
VL - 26
SP - 1016
EP - 1026
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 7
ER -