Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report

Batel Blechter¹, Chao Agnes Hsiung², Xiaoyu Wang³, Haoyu Zhang³, Wei Jie Seow⁴, Jianxin Shi³, Nilanjan Chatterjee⁵, Hee Nam Kim⁶, Maria Pik Wong⁷, Yun-Chul Hong⁸, Jason Y Y Wong⁹, Juncheng Dai¹⁰, H Dean Hosgood¹¹, Zhaoming Wang¹², I-Shou Chang¹³, Jiyeon Choi³, Jiucun Wang¹⁴, Minsun Song¹⁵, Wei Hu³, Wei Zheng¹⁶, Jin Hee Kim¹⁷, Baosen Zhou¹⁸, Demetrius Albanes³, Min-Ho Shin⁸, Lap Ping Chung⁷, She-Juan An¹⁹, Hong Zheng²⁰, Yasushi Yatabe²¹, Xu-Chao Zhang¹⁹, Young Tae Kim²², Xiao-Ou Shu¹⁶, Young-Chul Kim²³, Roel C H Vermeulen²⁴, Bryan A Bassig²⁵, Jiang Chang²⁶, James Chung Man Ho²⁷, Bu-Tian Ji³, Michiaki Kubo²⁸, Yataro Daigo²⁹, Yukihide Momozawa²⁸, Yoichiro Kamatani³⁰, Takayuki Honda³¹, Hideo Kunitoh³², Shun-Ichi Watanabe³³, Yohei Miyagi³⁴, Haruhiko Nakayama³⁵, Shingo Matsumoto³⁶, Masahiro Tsuboi³⁷, Koichi Goto³⁶, Zhihua Yin³⁸, Atsushi Takahashi³⁰, Akiteru Goto³⁹, Yoshihiro Minamiya⁴⁰, Kimihiro Shimizu⁴¹, Kazumi Tanaka⁴², Tangchun Wu⁴³, Fusheng Wei⁴⁴, Jian Su¹⁹, Yeul Hong Kim⁴⁵, In-Jae Oh²³, Victor Ho Fun Lee⁴⁶, Wu-Chou Su⁴⁷, Yuh-Min Chen⁴⁸, Gee-Chen Chang⁴⁹, Kuan-Yu Chen⁵⁰, Ming-Shyan Huang⁵¹, Hsien-Chih Lin², Adeline Seow⁵², Jae Yong Park⁵³, Sun-Seog Kweon⁵⁴, Chien-Jen Chen⁵⁵, Yu-Tang Gao⁵⁶, Chen Wu⁵⁷, Biyun Qian²⁰, Daru Lu¹⁴, Jianjun Liu⁵⁸, Hyo-Sung Jeon⁵⁹, Chin-Fu Hsiao², Jae Sook Sung⁴⁵, Ying-Huang Tsai⁶⁰, Yoo Jin Jung⁶¹, Huan Guo⁶², Zhibin Hu¹⁰, Tzu-Yu Chen², Laurie Burdett⁶³, Meredith Yeager⁶³, Amy Hutchinson⁶³, Sonja I Berndt³, Wei Wu³⁸, Junwen Wang⁶⁴, Jin Eun Choi⁵⁹, Kyong Hwa Park⁴⁵, Sook Whan Sung⁶⁵, Li Liu⁶⁶, Chang Hyun Kang⁶¹, Chung-Hsing Chen¹³, Jun Xu⁶⁷, Peng Guan⁶⁸, Wen Tan⁵⁷, Chih-Liang Wang⁶⁹, Alan Dart Loon Sihoe⁷⁰, Ying Chen⁷¹, Yi Young Choi⁵⁹, Jun Suk Kim⁷², Ho-Il Yoon⁷³, Qiuyin Cai¹⁶, In Kyu Park⁶¹, Ping Xu⁷⁴, Qincheng He⁷⁵, Chih-Yi Chen⁷⁶, Junjie Wu¹⁴, Wei-Yen Lim⁷¹, Kun-Chieh Chen⁷⁷, John K C Chan⁷⁸, Jihua Li⁷⁹, Hongyan Chen¹⁴, Chong-Jen Yu⁸⁰, Li Jin¹⁴, Joseph F Fraumeni Jr³, Jie Liu⁸¹, Maria Teresa Landi³, Taiki Yamaji⁸², Yang Yang⁸³, Belynda Hicks⁶³, Kathleen Wyatt⁶³, Shengchao A Li⁶³, Hongxia Ma⁸⁴, Bao Song⁸¹, Zhehai Wang⁸¹, Sensen Cheng⁸¹, Xuelian Li⁶⁸, Yangwu Ren⁶⁸, Motoki Iwasaki⁸⁵, Junjie Zhu⁹, Gening Jiang⁹, Ke Fei⁹, Guoping Wu¹⁹, Li-Hsin Chien⁸⁶, Fang-Yu Tsai⁸⁷, Jinming Yu⁸¹, Victoria L Stevens⁸⁸, Pan-Chyr Yang⁸⁹, Dongxin Lin⁷¹, Kexin Chen²⁰, Yi-Long Wu¹⁹, Keitaro Matsuo⁹⁰, Nathaniel Rothman³, Kouya Shiraishi⁹¹, Hongbing Shen⁹², Stephen J Chanock³, Takashi Kohno⁹¹, Qing Lan³

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. Electronic address: batel.blechter@nih.gov.
² Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
⁶ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁷ Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong.
⁸ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁹ Epidemiology and Community Health Branch, National Heart Lung and Blood Institute, Bethesda, Maryland.
¹⁰ Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
¹¹ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York.
¹² Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
¹³ National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
¹⁴ Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
¹⁵ Department of Statistics and Research Institute of Natural Sciences, Sookmyung Women's University, Seoul, Republic of Korea.
¹⁶ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
¹⁷ Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
¹⁸ Department of Clinical Epidemiology and Center of Evidence Based Medicine, The First Hospital of China Medical University, Shenyang, People's Republic of China.
¹⁹ Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China.
²⁰ Department of Epidemiology and Biostatistics, Key Laboratory of Prevention and Control of Human Major Diseases, Ministry of Education, National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
²¹ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
²² Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
²³ Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasuneup, Republic of Korea.
²⁴ Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
²⁵ Saville Cancer Screening and Prevention Center, Inova Schar Cancer Institute, Inova Health System, Fairfax, Virginia.
²⁶ Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
²⁷ Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
²⁸ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
²⁹ 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.
³⁰ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
³¹ Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
³² Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
³³ Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
³⁴ Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
³⁵ Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
³⁶ Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
³⁷ Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
³⁸ Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China.
³⁹ Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan.
⁴⁰ Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita, Japan.
⁴¹ Department of Surgery, Division of General Thoracic Surgery, Shinshu University School of Medicine Asahi, Nagano, Japan.
⁴² Department of Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan.
⁴³ 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, People's Republic of China.
⁴⁴ China National Environmental Monitoring Center, Beijing, People's Republic of China.
⁴⁵ Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
⁴⁶ Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
⁴⁷ Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴⁸ Department of Chest Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴⁹ 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.
⁵⁰ Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
⁵¹ Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University and Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵² Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
⁵³ Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
⁵⁴ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Jeonnam Regional Cancer Center, Chonnam National University, Hwasun, Republic of Korea.
⁵⁵ Genomic Research Center, Academia Sinica, Taipei, Taiwan.
⁵⁶ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China.
⁵⁷ 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, People's Republic of China.
⁵⁸ Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea; Department of Human Genetics, Genome Institute of Singapore, Singapore, Singapore; School of Life Sciences, Anhui Medical University, Hefei, People's Republic of China.
⁵⁹ Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
⁶⁰ Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan; Department of Pulmonary and Critical Care, Xiamen Chang Gung Hospital, Xiamen, People's Republic of China.
⁶¹ Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁶² 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, People's Republic of China.
⁶³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Rockville, Maryland.
⁶⁴ Division of Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, People's Republic of China; State Key LaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Chinaboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People's Republic of China.
⁶⁵ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People's Republic of China.
⁶⁶ Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
⁶⁷ School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
⁶⁸ Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China; Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, People's Republic of China.
⁶⁹ Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁷⁰ CUHK Medical Centre, Hong Kong, China.
⁷¹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
⁷² Department of Internal Medicine, Division of Medical Oncology, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
⁷³ Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
⁷⁴ Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, People's Republic of China.
⁷⁵ State Key LaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Chinaboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People's Republic of China.
⁷⁶ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁷⁷ Department of Internal Medicine, Division of Pulmonary Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁷⁸ Department of Pathology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China.
⁷⁹ Qujing Center for Diseases Control and Prevention, Qujing, People's Republic of China.
⁸⁰ Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
⁸¹ Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
⁸² Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
⁸³ Shanghai Pulmonary Hospital, Shanghai, People's Republic of China.
⁸⁴ Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Rockville, Maryland; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
⁸⁵ Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan; Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
⁸⁶ Department of Applied Mathematics, Chung Yuan Christian University, Chong-Li, Taiwan; Department of Applied Mathematics, National Dong Hwa University, Hualien, Taiwan.
⁸⁷ National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan; Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁸⁸ Laboratory Services, American Cancer Society, Decatur, Georgia.
⁸⁹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁹⁰ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁹¹ Division of Genome Biology, National Cancer Research Institute, Tokyo, Japan.
⁹² Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.

PMID: 39581378
DOI: 10.1016/j.jtho.2024.11.019

Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report

Batel Blechter et al. J Thorac Oncol. 2025 Apr.

. 2025 Apr;20(4):521-530.

doi: 10.1016/j.jtho.2024.11.019. Epub 2024 Nov 22.

Authors

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. Electronic address: batel.blechter@nih.gov.
² Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
⁶ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁷ Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong.
⁸ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁹ Epidemiology and Community Health Branch, National Heart Lung and Blood Institute, Bethesda, Maryland.
¹⁰ Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
¹¹ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York.
¹² Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
¹³ National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
¹⁴ Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
¹⁵ Department of Statistics and Research Institute of Natural Sciences, Sookmyung Women's University, Seoul, Republic of Korea.
¹⁶ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
¹⁷ Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
¹⁸ Department of Clinical Epidemiology and Center of Evidence Based Medicine, The First Hospital of China Medical University, Shenyang, People's Republic of China.
¹⁹ Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China.
²⁰ Department of Epidemiology and Biostatistics, Key Laboratory of Prevention and Control of Human Major Diseases, Ministry of Education, National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
²¹ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
²² Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
²³ Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasuneup, Republic of Korea.
²⁴ Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
²⁵ Saville Cancer Screening and Prevention Center, Inova Schar Cancer Institute, Inova Health System, Fairfax, Virginia.
²⁶ Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
²⁷ Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
²⁸ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
²⁹ 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.
³⁰ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
³¹ Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
³² Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
³³ Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
³⁴ Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
³⁵ Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
³⁶ Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
³⁷ Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
³⁸ Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China.
³⁹ Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan.
⁴⁰ Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita, Japan.
⁴¹ Department of Surgery, Division of General Thoracic Surgery, Shinshu University School of Medicine Asahi, Nagano, Japan.
⁴² Department of Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan.
⁴³ 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, People's Republic of China.
⁴⁴ China National Environmental Monitoring Center, Beijing, People's Republic of China.
⁴⁵ Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
⁴⁶ Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
⁴⁷ Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴⁸ Department of Chest Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴⁹ 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.
⁵⁰ Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
⁵¹ Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University and Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵² Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
⁵³ Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
⁵⁴ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Jeonnam Regional Cancer Center, Chonnam National University, Hwasun, Republic of Korea.
⁵⁵ Genomic Research Center, Academia Sinica, Taipei, Taiwan.
⁵⁶ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China.
⁵⁷ 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, People's Republic of China.
⁵⁸ Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea; Department of Human Genetics, Genome Institute of Singapore, Singapore, Singapore; School of Life Sciences, Anhui Medical University, Hefei, People's Republic of China.
⁵⁹ Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
⁶⁰ Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan; Department of Pulmonary and Critical Care, Xiamen Chang Gung Hospital, Xiamen, People's Republic of China.
⁶¹ Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁶² 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, People's Republic of China.
⁶³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Rockville, Maryland.
⁶⁴ Division of Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, People's Republic of China; State Key LaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Chinaboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People's Republic of China.
⁶⁵ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People's Republic of China.
⁶⁶ Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
⁶⁷ School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
⁶⁸ Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China; Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, People's Republic of China.
⁶⁹ Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁷⁰ CUHK Medical Centre, Hong Kong, China.
⁷¹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
⁷² Department of Internal Medicine, Division of Medical Oncology, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
⁷³ Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
⁷⁴ Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, People's Republic of China.
⁷⁵ State Key LaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Chinaboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People's Republic of China.
⁷⁶ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁷⁷ Department of Internal Medicine, Division of Pulmonary Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁷⁸ Department of Pathology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China.
⁷⁹ Qujing Center for Diseases Control and Prevention, Qujing, People's Republic of China.
⁸⁰ Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
⁸¹ Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
⁸² Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
⁸³ Shanghai Pulmonary Hospital, Shanghai, People's Republic of China.
⁸⁴ Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Rockville, Maryland; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
⁸⁵ Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan; Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
⁸⁶ Department of Applied Mathematics, Chung Yuan Christian University, Chong-Li, Taiwan; Department of Applied Mathematics, National Dong Hwa University, Hualien, Taiwan.
⁸⁷ National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan; Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁸⁸ Laboratory Services, American Cancer Society, Decatur, Georgia.
⁸⁹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁹⁰ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁹¹ Division of Genome Biology, National Cancer Research Institute, Tokyo, Japan.
⁹² Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.

PMID: 39581378
DOI: 10.1016/j.jtho.2024.11.019

Abstract

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the EGFR gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared with EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (odds ratio = 8.63, 95% confidence interval: 5.67-13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (odds ratio = 3.50, 95% confidence interval: 2.44-5.00) (p-heterogeneity = 3.66 × 10^-3). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.

Keywords: EGFR mutation; Lung adenocarcinoma; Never-smokers; Polygenic risk score.

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Conflict of interest statement

Disclosure The authors declare no conflict of interest.

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Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report

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Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report

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