Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer

Dezheng Huo; Ye Feng; Stephen Haddad; Yonglan Zheng; Song Yao; Yoo Jeong Han; Temidayo O. Ogundiran; Clement Adebamowo; Oladosu Ojengbede; Adeyinka G. Falusi; Wei Zheng; William Blot; Qiuyin Cai; Lisa Signorello; Esther M. John; Leslie Bernstein; Jennifer J. Hu; Regina G. Ziegler; Sarah Nyante; Elisa V. Bandera; Sue A. Ingles; Michael F. Press; Sandra L. Deming; Jorge L. Rodriguez-Gil; Katherine L. Nathanson; Susan M. Domchek; Timothy R. Rebbeck; Edward A. Ruiz-Narváez; Lara E. Sucheston-Campbell; Jeannette T. Bensen; Michael S. Simon; Anselm Hennis; Barbara Nemesure; M. Cristina Leske; Stefan Ambs; Lin S. Chen; Frank Qian; Eric R. Gamazon; Kathryn L. Lunetta; Nancy J. Cox; Stephen J. Chanock; Laurence N. Kolonel; Andrew F. Olshan; Christine B. Ambrosone; Olufunmilayo I. Olopade; Julie R. Palmer; Christopher A. Haiman

doi:10.1093/hmg/ddw305

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer

Dezheng Huo
, Ye Feng
, Stephen Haddad
, Yonglan Zheng
, Song Yao
, Yoo Jeong Han
, Temidayo O. Ogundiran
, Clement Adebamowo
, Oladosu Ojengbede
, Adeyinka G. Falusi
, Wei Zheng
, William Blot
, Qiuyin Cai
, Lisa Signorello
, Esther M. John
, Leslie Bernstein
, Jennifer J. Hu
, Regina G. Ziegler
, Sarah Nyante
, Elisa V. Bandera

Sue A. Ingles, Michael F. Press, Sandra L. Deming, Jorge L. Rodriguez-Gil, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Edward A. Ruiz-Narváez, Lara E. Sucheston-Campbell, Jeannette T. Bensen, Michael S. Simon, Anselm Hennis, Barbara Nemesure, M. Cristina Leske, Stefan Ambs, Lin S. Chen, Frank Qian, Eric R. Gamazon, Kathryn L. Lunetta, Nancy J. Cox, Stephen J. Chanock, Laurence N. Kolonel, Andrew F. Olshan, Christine B. Ambrosone, Olufunmilayo I. Olopade, Julie R. Palmer, Christopher A. Haiman

Family , Population and Preventative Medicine

The University of Chicago
University of Southern California
Boston University
Roswell Park Cancer Institute
University of Ibadan
University of Maryland, Baltimore
Vanderbilt University
National Institutes of Health
Cancer Prevention Institute of California
Stanford University
City of Hope National Med Center
University of Miami
University of North Carolina at Chapel Hill
Rutgers - The State University of New Jersey, New Brunswick
University of Pennsylvania
Harvard University
Ohio State University
Wayne State University
The University of the West Indies
Stony Brook University
University of Amsterdam
University of Hawai'i at Mānoa

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P=1.8×10 ^-8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR=1.30; P=2.4×10 ^-10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR=1.34; P=2.2×10 ^-8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

Original language	English
Pages (from-to)	4835-4846
Number of pages	12
Journal	Human Molecular Genetics
Volume	25
Issue number	21
DOIs	https://doi.org/10.1093/hmg/ddw305
State	Published - 2016

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Huo, D., Feng, Y., Haddad, S., Zheng, Y., Yao, S., Han, Y. J., Ogundiran, T. O., Adebamowo, C., Ojengbede, O., Falusi, A. G., Zheng, W., Blot, W., Cai, Q., Signorello, L., John, E. M., Bernstein, L., Hu, J. J., Ziegler, R. G., Nyante, S., ... Haiman, C. A. (2016). Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer. Human Molecular Genetics, 25(21), 4835-4846. https://doi.org/10.1093/hmg/ddw305

@article{1794b2e6da1241ba862202fd6222d429,

title = "Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer",

abstract = "Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95\% CI: 1.18-1.40; P=1.8{\texttimes}10 -8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR=1.30; P=2.4{\texttimes}10 -10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR=1.34; P=2.2{\texttimes}10 -8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.",

author = "Dezheng Huo and Ye Feng and Stephen Haddad and Yonglan Zheng and Song Yao and Han, \{Yoo Jeong\} and Ogundiran, \{Temidayo O.\} and Clement Adebamowo and Oladosu Ojengbede and Falusi, \{Adeyinka G.\} and Wei Zheng and William Blot and Qiuyin Cai and Lisa Signorello and John, \{Esther M.\} and Leslie Bernstein and Hu, \{Jennifer J.\} 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 Nathanson, \{Katherine L.\} and Domchek, \{Susan M.\} and Rebbeck, \{Timothy R.\} and Ruiz-Narv{\'a}ez, \{Edward A.\} and Sucheston-Campbell, \{Lara E.\} and Bensen, \{Jeannette T.\} and Simon, \{Michael S.\} and Anselm Hennis and Barbara Nemesure and \{Cristina Leske\}, M. and Stefan Ambs and Chen, \{Lin S.\} and Frank Qian and Gamazon, \{Eric R.\} and Lunetta, \{Kathryn L.\} and Cox, \{Nancy J.\} and Chanock, \{Stephen J.\} and Kolonel, \{Laurence N.\} and Olshan, \{Andrew F.\} and Ambrosone, \{Christine B.\} and Olopade, \{Olufunmilayo I.\} and Palmer, \{Julie R.\} and Haiman, \{Christopher A.\}",

note = "Publisher Copyright: {\textcopyright} The Author 2016. Published by Oxford University Press.",

year = "2016",

doi = "10.1093/hmg/ddw305",

language = "English",

volume = "25",

pages = "4835--4846",

journal = "Human Molecular Genetics",

issn = "0964-6906",

number = "21",

}

Huo, D, Feng, Y, Haddad, S, Zheng, Y, Yao, S, Han, YJ, Ogundiran, TO, Adebamowo, C, Ojengbede, O, Falusi, AG, Zheng, W, Blot, W, Cai, Q, Signorello, L, John, EM, Bernstein, L, Hu, JJ, Ziegler, RG, Nyante, S, Bandera, EV, Ingles, SA, Press, MF, Deming, SL, Rodriguez-Gil, JL, Nathanson, KL, Domchek, SM, Rebbeck, TR, Ruiz-Narváez, EA, Sucheston-Campbell, LE, Bensen, JT, Simon, MS, Hennis, A, Nemesure, B, Cristina Leske, M, Ambs, S, Chen, LS, Qian, F, Gamazon, ER, Lunetta, KL, Cox, NJ, Chanock, SJ, Kolonel, LN, Olshan, AF, Ambrosone, CB, Olopade, OI, Palmer, JR & Haiman, CA 2016, 'Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer', Human Molecular Genetics, vol. 25, no. 21, pp. 4835-4846. https://doi.org/10.1093/hmg/ddw305

TY - JOUR

T1 - Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer

AU - Huo, Dezheng

AU - Feng, Ye

AU - Haddad, Stephen

AU - Zheng, Yonglan

AU - Yao, Song

AU - Han, Yoo Jeong

AU - Ogundiran, Temidayo O.

AU - Adebamowo, Clement

AU - Ojengbede, Oladosu

AU - Falusi, Adeyinka G.

AU - Zheng, Wei

AU - Blot, William

AU - Cai, Qiuyin

AU - Signorello, Lisa

AU - John, Esther M.

AU - Bernstein, Leslie

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 - Nathanson, Katherine L.

AU - Domchek, Susan M.

AU - Rebbeck, Timothy R.

AU - Ruiz-Narváez, Edward A.

AU - Sucheston-Campbell, Lara E.

AU - Bensen, Jeannette T.

AU - Simon, Michael S.

AU - Hennis, Anselm

AU - Nemesure, Barbara

AU - Cristina Leske, M.

AU - Ambs, Stefan

AU - Chen, Lin S.

AU - Qian, Frank

AU - Gamazon, Eric R.

AU - Lunetta, Kathryn L.

AU - Cox, Nancy J.

AU - Chanock, Stephen J.

AU - Kolonel, Laurence N.

AU - Olshan, Andrew F.

AU - Ambrosone, Christine B.

AU - Olopade, Olufunmilayo I.

AU - Palmer, Julie R.

AU - Haiman, Christopher A.

PY - 2016

Y1 - 2016

N2 - Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P=1.8×10 -8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR=1.30; P=2.4×10 -10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR=1.34; P=2.2×10 -8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

AB - Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P=1.8×10 -8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR=1.30; P=2.4×10 -10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR=1.34; P=2.2×10 -8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

UR - https://www.scopus.com/pages/publications/85014866092

U2 - 10.1093/hmg/ddw305

DO - 10.1093/hmg/ddw305

M3 - Article

C2 - 28171663

AN - SCOPUS:85014866092

SN - 0964-6906

VL - 25

SP - 4835

EP - 4846

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 21

ER -

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer

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