Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

Xiang Shu¹, Jirong Long¹, Qiuyin Cai¹, Sun-Seog Kweon^{2

3}, Ji-Yeob Choi^{4

5

6}, Michiaki Kubo⁷, Sue K Park^{4

5

6}, Manjeet K Bolla⁸, Joe Dennis⁸, Qin Wang⁸, Yaohua Yang¹, Jiajun Shi¹, Xingyi Guo¹, Bingshan Li⁹, Ran Tao^{10

11}, Kristan J Aronson¹², Kelvin Y K Chan^{13

14}, Tsun L Chan^{15

16}, Yu-Tang Gao¹⁷, Mikael Hartman^{18

19

20}, Weang Kee Ho²¹, Hidemi Ito^{22

23}, Motoki Iwasaki²⁴, Hiroji Iwata²⁵, Esther M John^{26

27

28}, Yoshio Kasuga²⁹, Ui Soon Khoo¹³, Mi-Kyung Kim³⁰, Sun-Young Kong^{31

32

33}, Allison W Kurian²⁷, Ava Kwong^{15

34

35}, Eun-Sook Lee^{31

32

33}, Jingmei Li^{20

36

37}, Artitaya Lophatananon^{38

39}, Siew-Kee Low⁷, Shivaani Mariapun⁴⁰, Koichi Matsuda⁴¹, Keitaro Matsuo^{42

43}, Kenneth Muir^{38

39}, Dong-Young Noh^{6

44}, Boyoung Park⁴⁵, Min-Ho Park⁴⁶, Chen-Yang Shen^{47

48}, Min-Ho Shin², John J Spinelli^{49

50}, Atsushi Takahashi^{7

51}, Chiuchen Tseng⁵², Shoichiro Tsugane⁵³, Anna H Wu⁵², Yong-Bing Xiang¹⁷, Taiki Yamaji²⁴, Ying Zheng⁵⁴, Roger L Milne^{55

56

57}, Alison M Dunning⁵⁸, Paul D P Pharoah^{8

58}, Montserrat García-Closas⁵⁹, Soo-Hwang Teo^{40

60}, Xiao-Ou Shu¹, Daehee Kang^{5

6

61

62}, Douglas F Easton^{8

58}, Jacques Simard⁶³, Wei Zheng⁶⁴

Affiliations

¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
² Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.
³ Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea.
⁴ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
⁵ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁶ Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
⁷ RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁸ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁹ Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
¹⁰ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
¹¹ Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
¹² Department of Public Health Sciences and Queen's Cancer Research Institute, Queen's University, Kingston, ON, Canada.
¹³ Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
¹⁴ Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
¹⁵ Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR, China.
¹⁶ Department of Molecular Pathology, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China.
¹⁷ State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
¹⁸ Department of Surgery, National University Hospital, Singapore, Singapore.
¹⁹ Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
²⁰ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²¹ Department of Applied Mathematics, Faculty of Engineering, University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia.
²² Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan.
²³ Department of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
²⁴ Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
²⁵ Department of Breast Oncology, Aichi Cancer Center, Nagoya, Aichi, Japan.
²⁶ Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA.
²⁷ Departments of Health Research and Policy, School of Medicine, Stanford University, California, CA, USA.
²⁸ Stanford Cancer Institute, Stanford University School of Medicine, California, CA, USA.
²⁹ Department of Surgery, Nagano Matsushiro General Hospital, Nagano, Japan.
³⁰ Division of Cancer Epidemiology and Management, National Cancer Center, Goyang, Korea.
³¹ National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Republic of Korea.
³² Hospital, National Cancer Center, Goyang, Republic of Korea.
³³ Research Institute, National Cancer Center, Goyang, Republic of Korea.
³⁴ Department of Surgery, University of Hong Kong, Hong Kong SAR, China.
³⁵ Department of Surgery, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China.
³⁶ Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
³⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³⁸ Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
³⁹ Institute of Population Health, University of Manchester, Manchester, UK.
⁴⁰ Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
⁴¹ Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
⁴² Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁴³ Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴⁴ Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
⁴⁵ Department of Medicine, Hanyang University College of Medicine, Seoul, Korea.
⁴⁶ Department of Surgery, Chonnam National University Medical School, Seoul, Korea.
⁴⁷ College of Public Health, China Medical University, Taichong, Taiwan.
⁴⁸ Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
⁴⁹ Population Oncology, BC Cancer, Vancouver, BC, Canada.
⁵⁰ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
⁵¹ Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
⁵² Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵³ Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
⁵⁴ Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
⁵⁵ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
⁵⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia.
⁵⁷ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁵⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁵⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶⁰ Department of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpar, Malaysia.
⁶¹ Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
⁶² Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.
⁶³ Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, Canada.
⁶⁴ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. wei.zheng@vanderbilt.edu.

PMID: 32139696
PMCID: PMC7057957
DOI: 10.1038/s41467-020-15046-w

Meta-Analysis

Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

Xiang Shu et al. Nat Commun. 2020.

. 2020 Mar 5;11(1):1217.

doi: 10.1038/s41467-020-15046-w.

Authors

Affiliations

¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
² Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.
³ Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea.
⁴ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
⁵ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁶ Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
⁷ RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁸ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁹ Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
¹⁰ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
¹¹ Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
¹² Department of Public Health Sciences and Queen's Cancer Research Institute, Queen's University, Kingston, ON, Canada.
¹³ Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
¹⁴ Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
¹⁵ Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR, China.
¹⁶ Department of Molecular Pathology, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China.
¹⁷ State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
¹⁸ Department of Surgery, National University Hospital, Singapore, Singapore.
¹⁹ Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
²⁰ Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²¹ Department of Applied Mathematics, Faculty of Engineering, University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia.
²² Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan.
²³ Department of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
²⁴ Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
²⁵ Department of Breast Oncology, Aichi Cancer Center, Nagoya, Aichi, Japan.
²⁶ Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA.
²⁷ Departments of Health Research and Policy, School of Medicine, Stanford University, California, CA, USA.
²⁸ Stanford Cancer Institute, Stanford University School of Medicine, California, CA, USA.
²⁹ Department of Surgery, Nagano Matsushiro General Hospital, Nagano, Japan.
³⁰ Division of Cancer Epidemiology and Management, National Cancer Center, Goyang, Korea.
³¹ National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Republic of Korea.
³² Hospital, National Cancer Center, Goyang, Republic of Korea.
³³ Research Institute, National Cancer Center, Goyang, Republic of Korea.
³⁴ Department of Surgery, University of Hong Kong, Hong Kong SAR, China.
³⁵ Department of Surgery, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China.
³⁶ Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
³⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³⁸ Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
³⁹ Institute of Population Health, University of Manchester, Manchester, UK.
⁴⁰ Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
⁴¹ Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
⁴² Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁴³ Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴⁴ Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
⁴⁵ Department of Medicine, Hanyang University College of Medicine, Seoul, Korea.
⁴⁶ Department of Surgery, Chonnam National University Medical School, Seoul, Korea.
⁴⁷ College of Public Health, China Medical University, Taichong, Taiwan.
⁴⁸ Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
⁴⁹ Population Oncology, BC Cancer, Vancouver, BC, Canada.
⁵⁰ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
⁵¹ Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
⁵² Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵³ Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
⁵⁴ Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
⁵⁵ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
⁵⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia.
⁵⁷ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁵⁸ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁵⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁶⁰ Department of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpar, Malaysia.
⁶¹ Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
⁶² Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.
⁶³ Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, Canada.
⁶⁴ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. wei.zheng@vanderbilt.edu.

PMID: 32139696
PMCID: PMC7057957
DOI: 10.1038/s41467-020-15046-w

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.

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Conflict of interest statement

The authors declare no competing interests.

References

1. Torre LA, et al. Global cancer statistics, 2012. CA Cancer J. Clin. 2015;65:87–108. doi: 10.3322/caac.21262. - DOI - PubMed
1. Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. Ann. Oncol. 2015;26:1291–1299. doi: 10.1093/annonc/mdv022. - DOI - PMC - PubMed
1. Zheng W, et al. Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat. Genet. 2009;41:324–328. doi: 10.1038/ng.318. - DOI - PMC - PubMed
1. Cai Q, et al. Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1. Nat. Genet. 2014;46:886–890. doi: 10.1038/ng.3041. - DOI - PMC - PubMed
1. Wellcome Trust Case Control C. Genome-wide association study of 14,000 cases of seven common diseases and 3000 shared controls. Nature. 2007;447:661–678. doi: 10.1038/nature05911. - DOI - PMC - PubMed

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Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

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Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

Authors

Affiliations

Abstract

Conflict of interest statement

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