Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. jianxin.shi@nih.gov. Division of Genome Biology, National Cancer Research Institute, Tokyo, Japan. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China. Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China. Department of Clinical Epidemiology and Center of Evidence Based Medicine, The First Hospital of China Medical University, Shenyang, China. Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China. Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore. National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea. Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. Department of Biostatistics, Bioinformatics & Biomathematics, Georgetown University Medical Center, Washington, DC, USA. Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea. Shanghai Pulmonary Hospital, Shanghai, China. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan. Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasuneup, Republic of Korea. Department of Internal Medicine, Chonnam National Univerisity Medical School, Gwangju, Republic of Korea. Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Department of Medical Oncology and Cancer Center, and Center for Advanced Medicine against Cancer, Shiga University of Medical Science, Shiga, Japan. Department of Statistics & Research Institute of Natural Sciences, Sookmyung Women's University, Seoul, Republic of Korea. Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan. Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA. Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan. Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan. Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo, Japan. Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan. Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita, Japan. Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan. Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan. Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Department of Surgery, Division of General Thoracic Surgery, Shinshu University School of Medicine Asahi, Nagano, Japan. Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. Department of Integrative center of General Surgery, Gunma University Hospital, Gunma, Japan. Institute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China. China National Environmental Monitoring Center, Beijing, China. Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea. Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong. School of Medicine and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. Department of Internal Medicine, Division of Pulmonary Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan. Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan. Department of Internal Medicine, Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan. Department of Pulmonary and Critical Care, Xiamen Chang Gung Hospital, Xiamen, China. Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University and Kaohsiung Medical University, Kaohsiung, Taiwan. Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Department of Chest Medicine, Taipei Veterans General Hospital, and school of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. Jeonnam Regional Cancer Center, Chonnam National University, Hwasun, Republic of Korea. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China. Genome Institute of Singapore, Agency of Science, Technology and Research, Singapore, Singapore. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Karmanos Cancer Institute, Detroit, MI, USA. Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK. Department of Medicine, Section of Epidemiology and Population Science, Institute for Clinical and Translational Research, Houston, TX, USA. School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA. British Columbia Cancer Agency, Vancouver, BC, Canada. IUOPA, University of Oviedo and CIBERESP, Madrid, Spain. Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. International Agency for Research on Cancer (IARC/WHO), Lyon, France. German Cancer Research Center (DKFZ), Heidelberg, Germany. Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. University of Salzburg and Cancer Cluster Salzburg, Salzburg, Austria. University Medical Center Goettingen, Goettingen, Germany. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany. Helmholtz Center Munich, Institute of Epidemiology, Munich, Germany. Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany. Harvard TH Chan School of Public Health, Boston, MA, USA. Carmel Medical Center, Haifa, Israel. Markey Cancer Center, Lexington, KY, USA. Liverpool University, Liverpool, UK. The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA. Princess Margaret Cancer Center, Toronto, ON, Canada. Norris Cotton Cancer Center, Lebanon, NH, USA. Radboud University Medical Center, Nijmegen, Netherlands. National Institute of Occupational Health, Oslo, Norway. Department of Medical Biosciences, Umeå University, Umeå, Sweden. Department of Radiation Sciences, Umeå University, Umeå, Sweden. University of Sheffield, Sheffield, UK. UPMC Hillman Cancer Center and Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Washington State University College of Pharmacy, Spokane, WA, USA. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA. Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Rockville, MD, USA. Department of Biochemistry, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Centre for Genomic Sciences, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Department of Human Genetics, Genome Institute of Singapore, Singapore, Singapore. Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, China. The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China. Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan. Gleneagles Hong Kong Hospital, Hong Kong, China. Department of Internal Medicine, Division of Medical Oncology, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, China. Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China. Qujing Center for Diseases Control and Prevention, Qujing, China. Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan. Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan. Center for Global Health, National Cancer Institute, Bethesda, MD, USA. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan. Genomic Research Center, Academia Sinica, Taipei, Taiwan. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Laboratory Services, American Cancer Society, Atlanta, GA, USA. Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. qingl@mail.nih.gov.

Nature communications. 2023;(1):3043

Abstract

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Methodological quality

Publication Type : Meta-Analysis

Metadata