Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry

Feng, Ye; Rhie, Suhn K.; Huo, Dezheng; Ruiz-Narvaez, Edward A.; Haddad, Stephen A.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue Ann; 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; Stram, Daniel O.; Olopade, Olufunmilayo I.; Palmer, Julie R.; & Haiman, Christopher A. (2017). Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry. Cancer Epidemiology, Biomarkers & Prevention, 26(7), 1016-26. PMCID: PMC5500414

Feng, Ye; Rhie, Suhn K.; Huo, Dezheng; Ruiz-Narvaez, Edward A.; Haddad, Stephen A.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue Ann; 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; Stram, Daniel O.; Olopade, Olufunmilayo I.; Palmer, Julie R.; & Haiman, Christopher A. (2017). Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry. Cancer Epidemiology, Biomarkers & Prevention, 26(7), 1016-26. PMCID: PMC5500414

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BACKGROUND: Genome-wide association studies have identified ~100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Due to 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 odds ratios that were directionally consistent with those previously reported, of which twelve 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.




JOUR



Feng, Ye
Rhie, Suhn K.
Huo, Dezheng
Ruiz-Narvaez, Edward A.
Haddad, Stephen A.
Ambrosone, Christine B.
John, Esther M.
Bernstein, Leslie
Zheng, Wei
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah
Bandera, Elisa V.
Ingles, Sue Ann
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
Stram, Daniel O.
Olopade, Olufunmilayo I.
Palmer, Julie R.
Haiman, Christopher A.



2017


Cancer Epidemiology, Biomarkers & Prevention

26

7

1016-26








PMC5500414


10090

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