Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.
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.
Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Dezheng
D
Huo
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Ye
Y
Feng
Slone Epidemiology Center, Boston University, Boston, MA, USA.
Stephen
S
Haddad
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Yonglan
Y
Zheng
Roswell Park Cancer Institute, Buffalo, NY, USA.
Song
S
Yao
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Yoo-Jeong
YJ
Han
Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Temidayo O
TO
Ogundiran
Department of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, MD, USA.
Clement
C
Adebamowo
Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Oladosu
O
Ojengbede
Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Adeyinka G
AG
Falusi
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Wei
W
Zheng
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
William
W
Blot
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Qiuyin
Q
Cai
Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD, USA.
Lisa
L
Signorello
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.
Esther M
EM
John
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Leslie
L
Bernstein
Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Jennifer J
JJ
Hu
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA, USA.
Regina G
RG
Ziegler
Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Sarah
S
Nyante
The Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Elisa V
EV
Bandera
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Sue A
SA
Ingles
Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Michael F
MF
Press
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Sandra L
SL
Deming
Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Jorge L
JL
Rodriguez-Gil
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katherine L
KL
Nathanson
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Susan M
SM
Domchek
Dana Farber Cancer Institute & Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Timothy R
TR
Rebbeck
Slone Epidemiology Center, Boston University, Boston, MA, USA.
Edward A
EA
Ruiz-Narváez
Colleges of Pharmacy and Veterinary Medicine, Ohio State University, Columbus, OH, USA.
Lara E
LE
Sucheston-Campbell
Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Jeannette T
JT
Bensen
Karmanos Cancer Institute, Department of Oncology, Wayne State University, Detroit, MI, USA.
Michael S
MS
Simon
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.
Anselm
A
Hennis
Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.
Barbara
B
Nemesure
Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.
M Cristina
MC
Leske
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
Stefan
S
Ambs
Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Lin S
LS
Chen
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Frank
F
Qian
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.
Eric R
ER
Gamazon
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Kathryn L
KL
Lunetta
Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Nancy J
NJ
Cox
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA, USA.
Stephen J
SJ
Chanock
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Laurence N
LN
Kolonel
Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Andrew F
AF
Olshan
Roswell Park Cancer Institute, Buffalo, NY, USA.
Christine B
CB
Ambrosone
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
Olufunmilayo I
OI
Olopade
Slone Epidemiology Center, Boston University, Boston, MA, USA.
Julie R
JR
Palmer
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Christopher A
CA
Haiman
D001741:Black or African American / Q000235:genetics; D000483:Alleles; D044383:Black People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D012307:Risk Factors; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism
D011960:Receptors, Estrogen; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human