Abstract

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.

GWAS have enhanced our understanding for the genetic basis of breast cancer, but the majority of them were performed for European ancestry populations. Here, the authors use a cross-ancestry approach and report seven new variants associated with breast cancer risk among women of African ancestry.

Details

Title
Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women
Author
Adedokun Babatunde 1 ; Du, Zhaohui 2 ; Gao Guimin 3   VIAFID ORCID Logo  ; Ahearn, Thomas U 4   VIAFID ORCID Logo  ; Lunetta, Kathryn L 5   VIAFID ORCID Logo  ; Zirpoli, Gary 6 ; Figueroa Jonine 7   VIAFID ORCID Logo  ; John, Esther M 8 ; Bernstein, Leslie 9   VIAFID ORCID Logo  ; Zheng, Wei 10   VIAFID ORCID Logo  ; Hu, Jennifer J 11 ; Ziegler, Regina G 4   VIAFID ORCID Logo  ; Nyante, Sarah 12   VIAFID ORCID Logo  ; Bandera, Elisa V 13 ; Ingles, Sue A 2 ; Press, Michael F 14   VIAFID ORCID Logo  ; Deming-Halverson, Sandra L 10 ; Rodriguez-Gil, Jorge L 15   VIAFID ORCID Logo  ; Yao, Song 16   VIAFID ORCID Logo  ; Ogundiran, Temidayo O 17 ; Oladosu, Ojengbede 18 ; Blot, William 10 ; Troester, Melissa A 19 ; Nathanson, Katherine L 20   VIAFID ORCID Logo  ; Hennis Anselm 21 ; Nemesure, Barbara 22 ; Ambs, Stefan 23   VIAFID ORCID Logo  ; Fiorica, Peter N 3 ; Sucheston-Campbell, Lara E 24 ; Bensen, Jeannette T 19 ; Kushi, Lawrence H 25   VIAFID ORCID Logo  ; Torres-Mejia, Gabriela 26 ; Hu Donglei 27   VIAFID ORCID Logo  ; Fejerman Laura 27   VIAFID ORCID Logo  ; Bolla, Manjeet K 28 ; Dennis, Joe 28   VIAFID ORCID Logo  ; Dunning, Alison M 29   VIAFID ORCID Logo  ; Easton, Douglas F 30   VIAFID ORCID Logo  ; Michailidou Kyriaki 31 ; Pharoah Paul D P 30   VIAFID ORCID Logo  ; Wang, Qin 28 ; Sandler, Dale P 32   VIAFID ORCID Logo  ; Taylor, Jack A 32   VIAFID ORCID Logo  ; O’Brien Katie M 32 ; Kitahara, Cari M 33 ; Falusi, Adeyinka G 34 ; Babalola Chinedum 35   VIAFID ORCID Logo  ; Yarney Joel 36 ; Baffour, Awuah 37 ; Addai-Wiafe Beatrice 38 ; Chanock, Stephen J 4   VIAFID ORCID Logo  ; Olshan, Andrew F 19 ; Ambrosone, Christine B 16   VIAFID ORCID Logo  ; Conti, David V 2 ; Ziv Elad 27 ; Olopade, Olufunmilayo I 1   VIAFID ORCID Logo  ; Garcia-Closas, Montserrat 4   VIAFID ORCID Logo  ; Palmer, Julie R 6 ; Haiman, Christopher A 2   VIAFID ORCID Logo  ; Huo Dezheng 39   VIAFID ORCID Logo 

1  University of Chicago, Center for Clinical Cancer Genetics and Global Health, Department of Medicine, Chicago, USA (GRID:grid.170205.1) (ISNI:0000 0004 1936 7822) 
2  University of Southern California, Department of Preventative Medicine, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
3  University of Chicago, Department of Public Health Sciences, Chicago, USA (GRID:grid.170205.1) (ISNI:0000 0004 1936 7822) 
4  National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
5  Boston University School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
6  Boston University, Slone Epidemiology Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
7  University of Edinburgh, Usher Institute and CRUK Edinburgh Centre, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
8  Stanford University School of Medicine, Departments of Epidemiology & Population Health and of Medicine (Oncology) and Stanford Cancer Institute, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
9  City of Hope Comprehensive Cancer Center, Biomarkers of Early Detection and Prevention, Department of Population Sciences, Beckman Research Institute, Duarte, USA (GRID:grid.410425.6) (ISNI:0000 0004 0421 8357) 
10  Vanderbilt University, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
11  University of Miami, Department of Public Health Sciences, Miami, USA (GRID:grid.26790.3a) (ISNI:0000 0004 1936 8606) 
12  University of North Carolina, Department of Radiology, Chapel Hill, USA (GRID:grid.410711.2) (ISNI:0000 0001 1034 1720) 
13  Rutgers Cancer Institute of New Jersey, Cancer Prevention and Control Program, New Brunswick, USA (GRID:grid.430387.b) (ISNI:0000 0004 1936 8796) 
14  University of Southern California, Department of Pathology, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
15  National Human Genome Research Institute, NIH, Genomics, Development and Disease Section, Genetic Disease Research Branch, Bethesda, USA (GRID:grid.280128.1) (ISNI:0000 0001 2233 9230) 
16  Roswell Park Comprehensive Cancer Center, Department of Cancer Prevention and Control, Buffalo, USA (GRID:grid.240614.5) (ISNI:0000 0001 2181 8635) 
17  University of Ibadan, Department of Surgery, College of Medicine, Ibadan, Nigeria (GRID:grid.9582.6) (ISNI:0000 0004 1794 5983) 
18  University of Ibadan, Center for Population and Reproductive Health, College of Medicine, Ibadan, Nigeria (GRID:grid.9582.6) (ISNI:0000 0004 1794 5983) 
19  University of North Carolina, Department of Epidemiology, Gillings School of Global Public Health, Chapel Hill, USA (GRID:grid.410711.2) (ISNI:0000 0001 1034 1720) 
20  University of Pennsylvania, Department of Medicine, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
21  University of the West Indies, Bridgetown, Barbados (GRID:grid.412886.1); Stony Brook University, Department of Family, Population and Preventive Medicine, Stony Brook, USA (GRID:grid.36425.36) (ISNI:0000 0001 2216 9681) 
22  Stony Brook University, Department of Family, Population and Preventive Medicine, Stony Brook, USA (GRID:grid.36425.36) (ISNI:0000 0001 2216 9681) 
23  National Cancer Institute, Laboratory of Human Carcinogenesis, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
24  The Ohio State University, Department of Veterinary Biosciences, College of Veterinary Medicine, Columbus, USA (GRID:grid.261331.4) (ISNI:0000 0001 2285 7943) 
25  Kaiser Permanente Northern California, Division of Research, Oakland, USA (GRID:grid.280062.e) (ISNI:0000 0000 9957 7758) 
26  Instituto Nacional de Salud Publica, Center for Population Health Research, Cuernavaca, Mexico (GRID:grid.415771.1) (ISNI:0000 0004 1773 4764) 
27  University of California San Francisco, Department of Medicine, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
28  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
29  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
30  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
31  The Cyprus Institute of Neurology & Genetics, Biostatistics Unit, Nicosia, Cyprus (GRID:grid.417705.0) (ISNI:0000 0004 0609 0940) 
32  NIH, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
33  National Cancer Institute, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
34  University of Ibadan, Institute for Advanced Medical Research and Training, College of Medicine, Ibadan, Nigeria (GRID:grid.9582.6) (ISNI:0000 0004 1794 5983) 
35  University of Ibadan, Department of Pharmaceutical Chemistry, Ibadan, Nigeria (GRID:grid.9582.6) (ISNI:0000 0004 1794 5983) 
36  Korle Bu Teaching Hospital, Accra, Ghana (GRID:grid.415489.5) (ISNI:0000 0004 0546 3805) 
37  Komfo Anokye Teaching Hospital, Kumasi, Ghana (GRID:grid.415450.1) (ISNI:0000 0004 0466 0719) 
38  Peace and Love Hospital, Kumasi, Ghana (GRID:grid.415450.1) 
39  University of Chicago, Center for Clinical Cancer Genetics and Global Health, Department of Medicine, Chicago, USA (GRID:grid.170205.1) (ISNI:0000 0004 1936 7822); University of Chicago, Department of Public Health Sciences, Chicago, USA (GRID:grid.170205.1) (ISNI:0000 0004 1936 7822) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-021-24327-x
ProQuest document ID
2549110292
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.