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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1016-1026 |
| Number of pages | 11 |
| Journal | Cancer Epidemiology Biomarkers and Prevention |
| Volume | 26 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2017 |
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ASJC Scopus subject areas
- Epidemiology
- Oncology
Cite this
Characterizing genetic susceptibility to breast cancer in women of african ancestry. / Feng, Ye; Rhie, Suhn Kyong; Huo, Dezheng; Ruiz-Narvaez, Edward A.; Haddad, Stephen A.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Zheng, Yonglan; Yao, Song; Han, Yoo Jeong; Ogundiran, Temidayo O.; Rebbeck, Timothy R.; Adebamowo, Clement; Ojengbede, Oladosu; Falusi, Adeyinka G.; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Blot, William; Cai, Qiuyin; Signorello, Lisa; Nathanson, Katherine L.; Lunetta, Kathryn L.; Sucheston-Campbell, Lara E.; Bensen, Jeannette T.; Chanock, Stephen J.; Le Marchand, Loic; Olshan, Andrew F.; Kolonel, Laurence N.; Conti, David V.; Coetzee, Gerhard A.; Stram, Daniel O.; Olopade, Olufunmilayo I.; Palmer, Julie R.; Haiman, Christopher A.
In: Cancer Epidemiology Biomarkers and Prevention, Vol. 26, No. 7, 01.07.2017, p. 1016-1026.Research output: Contribution to journal › Article
}
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
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.
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 -