Abstract

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10−8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

Details

Title
Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants
Author
Xiang, Shu 1 ; Long, Jirong 1 ; Cai Qiuyin 1 ; Sun-Seog, Kweon 2 ; Choi Ji-Yeob 3 ; Kubo Michiaki 4 ; Park, Sue K 3   VIAFID ORCID Logo  ; Bolla, Manjeet K 5 ; Dennis, Joe 5   VIAFID ORCID Logo  ; Wang, Qin 5 ; Yang, Yaohua 1 ; Shi Jiajun 1   VIAFID ORCID Logo  ; Guo Xingyi 1 ; Li Bingshan 6   VIAFID ORCID Logo  ; Tao Ran 7 ; Aronson, Kristan J 8 ; Chan Kelvin Y K 9 ; Chan, Tsun L 10 ; Yu-Tang, Gao 11 ; Hartman, Mikael 12 ; Kee Ho Weang 13 ; Ito Hidemi 14   VIAFID ORCID Logo  ; Iwasaki Motoki 15 ; Iwata Hiroji 16 ; John, Esther M 17 ; Kasuga Yoshio 18 ; Soon Khoo Ui 19 ; Kim, Mi-Kyung 20   VIAFID ORCID Logo  ; Sun-Young, Kong 21   VIAFID ORCID Logo  ; Kurian, Allison W 22 ; Kwong Ava 23 ; Lee, Eun-Sook 21   VIAFID ORCID Logo  ; Li, Jingmei 24   VIAFID ORCID Logo  ; Artitaya, Lophatananon 25 ; Siew-Kee, Low 26   VIAFID ORCID Logo  ; Shivaani, Mariapun 27 ; Matsuda Koichi 28   VIAFID ORCID Logo  ; Matsuo Keitaro 29   VIAFID ORCID Logo  ; Muir, Kenneth 25   VIAFID ORCID Logo  ; Dong-Young, Noh 30 ; Park, Boyoung 31 ; Min-Ho, Park 32   VIAFID ORCID Logo  ; Chen-Yang, Shen 33 ; Min-Ho, Shin 34 ; Spinelli, John J 35   VIAFID ORCID Logo  ; Takahashi, Atsushi 36 ; Tseng Chiuchen 37 ; Tsugane Shoichiro 38   VIAFID ORCID Logo  ; Wu, Anna H 37 ; Yong-Bing, Xiang 11 ; Yamaji Taiki 15 ; Zheng, Ying 39 ; Milne, Roger L 40   VIAFID ORCID Logo  ; Dunning, Alison M 41   VIAFID ORCID Logo  ; Pharoah Paul D P 42   VIAFID ORCID Logo  ; García-Closas Montserrat 43   VIAFID ORCID Logo  ; Soo-Hwang, Teo 44   VIAFID ORCID Logo  ; Xiao-ou, Shu 1 ; Kang Daehee 45 ; Easton, Douglas F 42   VIAFID ORCID Logo  ; Simard, Jacques 46   VIAFID ORCID Logo  ; Zheng, Wei 1   VIAFID ORCID Logo 

1  Vanderbilt University Medical Center, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916) 
2  Chonnam National University Medical School, Department of Preventive Medicine, Hwasun, Korea (GRID:grid.14005.30) (ISNI:0000 0001 0356 9399); Chonnam National University Hwasun Hospital, Jeonnam Regional Cancer Center, Hwasun, Korea (GRID:grid.411602.0) (ISNI:0000 0004 0647 9534) 
3  Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
4  RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (GRID:grid.31501.36) 
5  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
6  Vanderbilt Genetics Institute, Vanderbilt University, Department of Molecular Physiology & Biophysics, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
7  Vanderbilt University Medical Center, Department of Biostatistics, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916); Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916) 
8  Queen’s University, Department of Public Health Sciences and Queen’s Cancer Research Institute, Kingston, Canada (GRID:grid.410356.5) (ISNI:0000 0004 1936 8331) 
9  University of Hong Kong, Department of Pathology, Li Ka Shing Faculty of Medicine, Hong Kong SAR, China (GRID:grid.194645.b) (ISNI:0000000121742757); University of Hong Kong, Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, Hong Kong SAR, China (GRID:grid.194645.b) (ISNI:0000000121742757) 
10  Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR, China (GRID:grid.194645.b); Hong Kong Sanatorium & Hospital, Department of Molecular Pathology, Hong Kong SAR, China (GRID:grid.414329.9) (ISNI:0000 0004 1764 7097) 
11  Shanghai Jiaotong University School of Medicine, State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293) 
12  National University Hospital, Department of Surgery, Singapore, Singapore (GRID:grid.412106.0) (ISNI:0000 0004 0621 9599); Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University of Singapore, Department of Surgery, Yong Loo Lin School of Medicine, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
13  University of Nottingham Malaysia Campus, Department of Applied Mathematics, Faculty of Engineering, Semenyih, Malaysia (GRID:grid.440435.2) 
14  Aichi Cancer Center Research Institute, Division of Cancer Information and Control, Nagoya, Japan (GRID:grid.410800.d) (ISNI:0000 0001 0722 8444); Nagoya University Graduate School of Medicine, Department of Descriptive Cancer Epidemiology, Nagoya, Japan (GRID:grid.27476.30) (ISNI:0000 0001 0943 978X) 
15  Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
16  Aichi Cancer Center, Department of Breast Oncology, Nagoya, Japan (GRID:grid.410800.d) (ISNI:0000 0001 0722 8444) 
17  Cancer Prevention Institute of California, Department of Epidemiology, Fremont, USA (GRID:grid.280669.3) (ISNI:0000 0004 0498 8300); School of Medicine, Stanford University, Departments of Health Research and Policy, California, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford Cancer Institute, Stanford University School of Medicine, California, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
18  Nagano Matsushiro General Hospital, Department of Surgery, Nagano, Japan (GRID:grid.452634.2) 
19  University of Hong Kong, Department of Pathology, Li Ka Shing Faculty of Medicine, Hong Kong SAR, China (GRID:grid.194645.b) (ISNI:0000000121742757) 
20  Division of Cancer Epidemiology and Management, National Cancer Center, Goyang, Korea (GRID:grid.410914.9) (ISNI:0000 0004 0628 9810) 
21  National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Republic of Korea (GRID:grid.410914.9) (ISNI:0000 0004 0628 9810); Hospital, National Cancer Center, Goyang, Republic of Korea (GRID:grid.410914.9) (ISNI:0000 0004 0628 9810); Research Institute, National Cancer Center, Goyang, Republic of Korea (GRID:grid.410914.9) (ISNI:0000 0004 0628 9810) 
22  School of Medicine, Stanford University, Departments of Health Research and Policy, California, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
23  Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR, China (GRID:grid.168010.e); University of Hong Kong, Department of Surgery, Hong Kong SAR, China (GRID:grid.194645.b) (ISNI:0000000121742757); Hong Kong Sanatorium & Hospital, Department of Surgery, Hong Kong SAR, China (GRID:grid.414329.9) (ISNI:0000 0004 1764 7097) 
24  National University of Singapore, Department of Surgery, Yong Loo Lin School of Medicine, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); Human Genetics, Genome Institute of Singapore, Singapore, Singapore (GRID:grid.418377.e) (ISNI:0000 0004 0620 715X); Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
25  Warwick University, Division of Health Sciences, Warwick Medical School, Coventry, UK (GRID:grid.7372.1) (ISNI:0000 0000 8809 1613); Institute of Population Health, University of Manchester, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407) 
26  RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (GRID:grid.5379.8) 
27  Cancer Research Malaysia, Subang Jaya, Malaysia (GRID:grid.5379.8) 
28  University of Tokyo, Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
29  Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan (GRID:grid.410800.d) (ISNI:0000 0001 0722 8444); Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan (GRID:grid.27476.30) (ISNI:0000 0001 0943 978X) 
30  Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University Hospital, Department of Surgery, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X) 
31  Hanyang University College of Medicine, Department of Medicine, Seoul, Korea (GRID:grid.49606.3d) (ISNI:0000 0001 1364 9317) 
32  Chonnam National University Medical School, Department of Surgery, Seoul, Korea (GRID:grid.14005.30) (ISNI:0000 0001 0356 9399) 
33  China Medical University, College of Public Health, Taichong, Taiwan (GRID:grid.254145.3) (ISNI:0000 0001 0083 6092); Taiwan Biobank, Institute of Biomedical Sciences, Taipei, Taiwan (GRID:grid.28665.3f) (ISNI:0000 0001 2287 1366) 
34  Chonnam National University Medical School, Department of Preventive Medicine, Hwasun, Korea (GRID:grid.14005.30) (ISNI:0000 0001 0356 9399) 
35  Population Oncology, BC Cancer, Vancouver, Canada (GRID:grid.14005.30); University of British Columbia, School of Population and Public Health, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
36  RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (GRID:grid.17091.3e); Research Institute, National Cerebral and Cardiovascular Center, Department of Genomic Medicine, Suita, Japan (GRID:grid.410796.d) (ISNI:0000 0004 0378 8307) 
37  University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
38  National Cancer Center, Center for Public Health Sciences, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
39  Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China (GRID:grid.430328.e) 
40  Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia (GRID:grid.3263.4) (ISNI:0000 0001 1482 3639); Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
41  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
42  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) 
43  National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
44  Cancer Research Malaysia, Subang Jaya, Malaysia (GRID:grid.48336.3a); University Malaya, Department of Surgery, Faculty of Medicine, Kuala Lumpar, Malaysia (GRID:grid.10347.31) (ISNI:0000 0001 2308 5949) 
45  Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University Graduate School, Department of Biomedical Sciences, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X) 
46  Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, Canada (GRID:grid.63984.30) (ISNI:0000 0000 9064 4811) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-15046-w
ProQuest document ID
2371802940
Copyright
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.