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  • PMID: 27594435 was deleted because it is a duplicate of PMID: 28171663
Hum Mol Genet. 2016 Nov 1;25(21):4835-4846. 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.

Author information

1
Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
2
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
3
Slone Epidemiology Center, Boston University, Boston, MA, USA.
4
Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
5
Roswell Park Cancer Institute, Buffalo, NY, USA.
6
Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria.
7
Department of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, MD, USA.
8
Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
9
Institute for Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.
10
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
11
Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD, USA.
12
Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
13
Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
14
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA, USA.
15
Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
16
The Cancer Institute of New Jersey, New Brunswick, NJ, USA.
17
Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
18
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
19
Dana Farber Cancer Institute & Harvard T.H. Chan School of Public Health, Boston, MA, USA.
20
Colleges of Pharmacy and Veterinary Medicine, Ohio State University, Columbus, OH, USA.
21
Karmanos Cancer Institute, Department of Oncology, Wayne State University, Detroit, MI, USA.
22
Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.
23
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
24
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
25
Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
26
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.

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.

PMID:
28171663
PMCID:
PMC5975608
DOI:
10.1093/hmg/ddw305
[Indexed for MEDLINE]

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