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Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics

Jia G 1 , Ping J 1 , Shu X 2 , Yang Y 1 , Cai Q 1 , Kweon SS 3 Show all authors , Choi JY 4 , Kubo M 5 , Park SK 4 , Bolla MK 6 , Dennis J 6 , Wang Q 6 , Guo X 1 , Li B 7 , Tao R 8 , Aronson KJ 9 , Chan TL 10 , Gao YT 11 , Hartman M 12 , Ho WK 13 , Ito H 14 , Iwasaki M 15 , Iwata H 16 , John EM 17 , Kasuga Y 18 , Kim MK 19 , Kurian AW 20 , Kwong A 21 , Li J 22 , Lophatananon A 23 , Low SK 5 , Mariapun S 24 , Matsuda K 25 , Matsuo K 26 , Muir K 23 , Noh DY 27 , Park B 28 , Park MH 29 , Shen CY 30 , Shin MH 31 , Spinelli JJ 32 , Takahashi A 33 , Tseng C 34 , Tsugane S 35 , Wu AH 34 , Yamaji T 15 , Zheng Y 36 , Dunning AM 37 , Pharoah PDP 38 , Teo SH 39 , Kang D 40 , Easton DF 38 , Simard J 41 , Shu XO 1 , Long J 1 , Zheng W 42

Affiliations 

  • 1 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, USA
  • 2 Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • 3 Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea; Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea
  • 4 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 5 RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 6 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 7 Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA
  • 8 Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
  • 9 Department of Public Health Sciences and Queen's Cancer Research Institute, Queen's University, Kingston, ON, Canada
  • 10 Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR, China; Department of Molecular Pathology, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China
  • 11 State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
  • 12 Department of Surgery, National University Hospital, Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • 13 Department of Applied Mathematics, Faculty of Engineering, University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia
  • 14 Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan; Department of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 15 Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
  • 16 Department of Breast Oncology, Aichi Cancer Center, Nagoya, Aichi, Japan
  • 17 Departments of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA; Departments of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
  • 18 Department of Surgery, Nagano Matsushiro General Hospital, Nagano, Japan
  • 19 Division of Cancer Epidemiology and Management, National Cancer Center, Goyang, Korea
  • 20 Departments of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA, USA
  • 21 Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR, China; Department of Surgery, University of Hong Kong, Hong Kong SAR, China; Department of Surgery, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China
  • 22 Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Human Genetics, Genome Institute of Singapore, Singapore, Singapore; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 23 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK; Institute of Population Health, University of Manchester, Manchester, UK
  • 24 Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia
  • 25 Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
  • 26 Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan; Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 27 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University Hospital, Seoul, South Korea
  • 28 Department of Medicine, Hanyang University College of Medicine, Seoul, Korea
  • 29 Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
  • 30 College of Public Health, China Medical University, Taichong, Taiwan; Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  • 31 Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea
  • 32 Department of Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
  • 33 RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
  • 34 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 35 National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan
  • 36 Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
  • 37 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
  • 38 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
  • 39 Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia; Department of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpar, Malaysia
  • 40 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea
  • 41 Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval, Research Center, Québec City, QC, Canada
  • 42 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, USA. Electronic address: wei.zheng@vanderbilt.edu
Am J Hum Genet, 2022 Dec 01;109(12):2185-2195.
PMID: 36356581 DOI: 10.1016/j.ajhg.2022.10.011

Abstract

By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p 

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