Environment International (Feb 2021)
Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia
- Batel Blechter,
- Jason Y.Y. Wong,
- Chao Agnes Hsiung,
- H.Dean Hosgood,
- Zhihua Yin,
- Xiao-Ou Shu,
- Han Zhang,
- Jianxin Shi,
- Lei Song,
- Minsun Song,
- Wei Zheng,
- Zhaoming Wang,
- Neil Caporaso,
- Laurie Burdette,
- Meredith Yeager,
- Sonja I. Berndt,
- Maria Teresa Landi,
- Chien-Jen Chen,
- Gee-Chen Chang,
- Chin-Fu Hsiao,
- Ying-Huang Tsai,
- Kuan-Yu Chen,
- Ming-Shyan Huang,
- Wu-Chou Su,
- Yuh-Min Chen,
- Li-Hsin Chien,
- Chung-Hsing Chen,
- Tsung-Ying Yang,
- Chih-Liang Wang,
- Jen-Yu Hung,
- Chien-Chung Lin,
- Reury-Perng Perng,
- Chih-Yi Chen,
- Kun-Chieh Chen,
- Yao-Jen Li,
- Chong-Jen Yu,
- Yi-Song Chen,
- Ying-Hsiang Chen,
- Fang-Yu Tsai,
- Wei Jie Seow,
- Bryan A. Bassig,
- Wei Hu,
- Bu-Tian Ji,
- Wei Wu,
- Peng Guan,
- Qincheng He,
- Yu-Tang Gao,
- Qiuyin Cai,
- Wong-Ho Chow,
- Yong-Bing Xiang,
- Dongxin Lin,
- Chen Wu,
- Yi-Long Wu,
- Min-Ho Shin,
- Yun-Chul Hong,
- Keitaro Matsuo,
- Kexin Chen,
- Maria Pik Wong,
- Daru Lu,
- Li Jin,
- Jiu-Cun Wang,
- Adeline Seow,
- Tangchun Wu,
- Hongbing Shen,
- Joseph F. Fraumeni,
- Pan-Chyr Yang,
- I-Shou Chang,
- Baosen Zhou,
- Stephen J. Chanock,
- Nathaniel Rothman,
- Nilanjan Chatterjee,
- Qing Lan
Affiliations
- Batel Blechter
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Corresponding author at: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21202, United States.
- Jason Y.Y. Wong
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Chao Agnes Hsiung
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- H.Dean Hosgood
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
- Zhihua Yin
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People’s Republic of China
- Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Han Zhang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Jianxin Shi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Lei Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Minsun Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA; Department of Statistics, Sookmyung Women's University, Seoul, Republic of Korea
- Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Zhaoming Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
- Neil Caporaso
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Laurie Burdette
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Leidos Biomedical Research, Inc., Frederick, MD, USA
- Meredith Yeager
- Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
- Sonja I. Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Maria Teresa Landi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Chien-Jen Chen
- Genomic Research Center, Academia Sinica, Taipei, Taiwan
- Gee-Chen Chang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Chin-Fu Hsiao
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- Ying-Huang Tsai
- Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
- Kuan-Yu Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Ming-Shyan Huang
- Department of Internal Medicine, E-Da Cancer Hospital, School of Medicine, I-Shou University, Kaohsiung, Taiwan
- Wu-Chou Su
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Yuh-Min Chen
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Li-Hsin Chien
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- Chung-Hsing Chen
- National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan
- Tsung-Ying Yang
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Chih-Liang Wang
- Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Jen-Yu Hung
- Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Chien-Chung Lin
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Reury-Perng Perng
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Chih-Yi Chen
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
- Kun-Chieh Chen
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Yao-Jen Li
- Genomic Research Center, Academia Sinica, Taipei, Taiwan
- Chong-Jen Yu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Yi-Song Chen
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- Ying-Hsiang Chen
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- Fang-Yu Tsai
- National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan
- Wei Jie Seow
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Bryan A. Bassig
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Wei Hu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Bu-Tian Ji
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Wei Wu
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People’s Republic of China
- Peng Guan
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People’s Republic of China
- Qincheng He
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People’s Republic of China
- Yu-Tang Gao
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People’s Republic of China
- Qiuyin Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Wong-Ho Chow
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Yong-Bing Xiang
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People’s Republic of China
- Dongxin Lin
- 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
- Chen Wu
- 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
- Yi-Long Wu
- Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
- Min-Ho Shin
- Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
- Yun-Chul Hong
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Keitaro Matsuo
- Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
- Kexin Chen
- Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China
- Maria Pik Wong
- Department of Pathology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong
- Daru Lu
- 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
- Li Jin
- 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
- Jiu-Cun Wang
- 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
- Adeline Seow
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
- Tangchun Wu
- 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
- Hongbing Shen
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China
- Joseph F. Fraumeni
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Pan-Chyr Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- I-Shou Chang
- National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan
- Baosen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People’s Republic of China
- Stephen J. Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Nathaniel Rothman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Nilanjan Chatterjee
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Qing Lan
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Journal volume & issue
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Vol. 147
p. 105975
Abstract
We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
