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PMID: 28171663 Published · ppublish English Journal Article Meta-Analysis

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 ·2016-00-01 ·Pages 4835-4846

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, Leske MC, 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

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, 26.5 Kb 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.

MeSH Terms
African Americans/genetics Alleles Blacks/genetics Breast Neoplasms/genetics Case-Control Studies Chromosomes, Human, Pair 3/genetics Female Gene Frequency/genetics Genetic Loci Genetic Predisposition to Disease/genetics Genome-Wide Association Study/methods Humans Polymorphism, Single Nucleotide/genetics Receptors, Estrogen/genetics Risk Factors TNF-Related Apoptosis-Inducing Ligand/genetics,metabolism
Chemicals
Receptors, Estrogen TNF-Related Apoptosis-Inducing Ligand TNFSF10 protein, human
Authors & Affiliations
47 authors, click to expand affiliations / ORCID
Huo Dezheng
Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Feng Ye
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Haddad Stephen
Slone Epidemiology Center, Boston University, Boston, MA, USA.
Zheng Yonglan
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Yao Song
Roswell Park Cancer Institute, Buffalo, NY, USA.
Han Yoo-Jeong
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Ogundiran Temidayo O
Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Adebamowo Clement
Department of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, MD, USA.
Ojengbede Oladosu
Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Falusi Adeyinka G
Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Zheng Wei
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Blot William
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Cai Qiuyin
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Signorello Lisa
Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD, USA.
John Esther M
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. | Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD, USA.
Bernstein Leslie
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Hu Jennifer J
Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Ziegler Regina G
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA, USA.
Nyante Sarah
Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Bandera Elisa V
The Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Ingles Sue A
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Press Michael F
Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Deming Sandra L
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Rodriguez-Gil Jorge L
Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Nathanson Katherine L
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Domchek Susan M
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rebbeck Timothy R
Dana Farber Cancer Institute & Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Ruiz-Narváez Edward A
Slone Epidemiology Center, Boston University, Boston, MA, USA.
Sucheston-Campbell Lara E
Colleges of Pharmacy and Veterinary Medicine, Ohio State University, Columbus, OH, USA.
Bensen Jeannette T
Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Simon Michael S
Karmanos Cancer Institute, Department of Oncology, Wayne State University, Detroit, MI, USA.
Hennis Anselm
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA. | Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Nemesure Barbara
Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.
Leske M Cristina
Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.
Ambs Stefan
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
Chen Lin S
Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Qian Frank
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Gamazon Eric R
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA, USA. | Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Lunetta Kathryn L
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Cox Nancy J
Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Chanock Stephen J
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA, USA.
Kolonel Laurence N
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Olshan Andrew F
Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Ambrosone Christine B
Roswell Park Cancer Institute, Buffalo, NY, USA.
Olopade Olufunmilayo I
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Palmer Julie R
Slone Epidemiology Center, Boston University, Boston, MA, USA.
Haiman Christopher A
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
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Article Info
Journal
Human molecular genetics
Abbr.
Hum Mol Genet
ISSN
1460-2083
DOI
10.1093/hmg/ddw305
Published
2016-00-01
Pages
4835-4846
Language
English
Region
England
NLM ID
9208958
PMCID
PMC5975608
Subset
IM
Grants
NCI NIH HHS · P30 CA016086 · United States
NIEHS NIH HHS · P30 ES010126 · United States
NIGMS NIH HHS · T32 GM008692 · United States
NCI NIH HHS · R01 CA092447 · United States
NCI NIH HHS · UM1 CA164974 · United States
External Links
PubMed source DOI: 10.1093/hmg/ddw305 PMC Full Text View journal details
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