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 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 HanTemidayo 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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1016-1026
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2017

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Genetic Predisposition to Disease
Breast Neoplasms
Alleles
Genetic Markers
Genome-Wide Association Study
Linkage Disequilibrium
Chromatin
Population

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Feng, Y., Rhie, S. K., Huo, D., Ruiz-Narvaez, E. A., Haddad, S. A., Ambrosone, C. B., ... Haiman, C. A. (2017). Characterizing genetic susceptibility to breast cancer in women of african ancestry. Cancer Epidemiology Biomarkers and Prevention, 26(7), 1016-1026. https://doi.org/10.1158/1055-9965.EPI-16-0567

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 journalArticle

Feng, Y, Rhie, SK, Huo, D, Ruiz-Narvaez, EA, Haddad, SA, Ambrosone, CB, John, EM, Bernstein, L, Zheng, W, Hu, J, Ziegler, RG, Nyante, S, Bandera, EV, Ingles, SA, Press, MF, Deming, SL, Rodriguez-Gil, JL, Zheng, Y, Yao, S, Han, YJ, Ogundiran, TO, Rebbeck, TR, Adebamowo, C, Ojengbede, O, Falusi, AG, Hennis, A, Nemesure, B, Ambs, S, Blot, W, Cai, Q, Signorello, L, Nathanson, KL, Lunetta, KL, Sucheston-Campbell, LE, Bensen, JT, Chanock, SJ, Le Marchand, L, Olshan, AF, Kolonel, LN, Conti, DV, Coetzee, GA, Stram, DO, Olopade, OI, Palmer, JR & Haiman, CA 2017, 'Characterizing genetic susceptibility to breast cancer in women of african ancestry', Cancer Epidemiology Biomarkers and Prevention, vol. 26, no. 7, pp. 1016-1026. https://doi.org/10.1158/1055-9965.EPI-16-0567
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. / Characterizing genetic susceptibility to breast cancer in women of african ancestry. In: Cancer Epidemiology Biomarkers and Prevention. 2017 ; Vol. 26, No. 7. pp. 1016-1026.
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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.",
author = "Ye Feng and Rhie, {Suhn Kyong} and Dezheng Huo and Ruiz-Narvaez, {Edward A.} and Haddad, {Stephen A.} and Ambrosone, {Christine B.} and John, {Esther M.} and Leslie Bernstein and Wei Zheng and Jennifer Hu and Ziegler, {Regina G.} and Sarah Nyante and Bandera, {Elisa V.} and Ingles, {Sue A.} and Press, {Michael F.} and Deming, {Sandra L.} and Rodriguez-Gil, {Jorge L.} and Yonglan Zheng and Song Yao and Han, {Yoo Jeong} and Ogundiran, {Temidayo O.} and Rebbeck, {Timothy R.} and Clement Adebamowo and Oladosu Ojengbede and Falusi, {Adeyinka G.} and Anselm Hennis and Barbara Nemesure and Stefan Ambs and William Blot and Qiuyin Cai and Lisa Signorello and Nathanson, {Katherine L.} and Lunetta, {Kathryn L.} and Sucheston-Campbell, {Lara E.} and Bensen, {Jeannette T.} and Chanock, {Stephen J.} and {Le Marchand}, Loic and Olshan, {Andrew F.} and Kolonel, {Laurence N.} and Conti, {David V.} and Coetzee, {Gerhard A.} and Stram, {Daniel O.} and Olopade, {Olufunmilayo I.} and Palmer, {Julie R.} and Haiman, {Christopher A.}",
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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.

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