. 2021 Feb:147:105975.

doi: 10.1016/j.envint.2020.105975. Epub 2020 Dec 29.

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

Batel Blechter¹, Jason Y Y Wong², Chao Agnes Hsiung³, H Dean Hosgood⁴, Zhihua Yin⁵, Xiao-Ou Shu⁶, Han Zhang², Jianxin Shi², Lei Song², Minsun Song⁷, Wei Zheng⁶, Zhaoming Wang⁸, Neil Caporaso², Laurie Burdette⁹, Meredith Yeager¹⁰, Sonja I Berndt², Maria Teresa Landi², Chien-Jen Chen¹¹, Gee-Chen Chang¹², Chin-Fu Hsiao³, Ying-Huang Tsai¹³, Kuan-Yu Chen¹⁴, Ming-Shyan Huang¹⁵, Wu-Chou Su¹⁶, Yuh-Min Chen¹⁷, Li-Hsin Chien³, Chung-Hsing Chen¹⁸, Tsung-Ying Yang¹⁹, Chih-Liang Wang²⁰, Jen-Yu Hung²¹, Chien-Chung Lin¹⁶, Reury-Perng Perng²², Chih-Yi Chen²³, Kun-Chieh Chen¹⁹, Yao-Jen Li¹¹, Chong-Jen Yu¹⁴, Yi-Song Chen³, Ying-Hsiang Chen³, Fang-Yu Tsai¹⁸, Wei Jie Seow²⁴, Bryan A Bassig², Wei Hu², Bu-Tian Ji², Wei Wu⁵, Peng Guan⁵, Qincheng He⁵, Yu-Tang Gao²⁵, Qiuyin Cai⁶, Wong-Ho Chow²⁶, Yong-Bing Xiang²⁵, Dongxin Lin²⁷, Chen Wu²⁷, Yi-Long Wu²⁸, Min-Ho Shin²⁹, Yun-Chul Hong³⁰, Keitaro Matsuo³¹, Kexin Chen³², Maria Pik Wong³³, Daru Lu³⁴, Li Jin³⁴, Jiu-Cun Wang³⁴, Adeline Seow³⁵, Tangchun Wu³⁶, Hongbing Shen³⁷, Joseph F Fraumeni², Pan-Chyr Yang¹⁴, I-Shou Chang¹⁸, Baosen Zhou⁵, Stephen J Chanock², Nathaniel Rothman², Nilanjan Chatterjee³⁸, Qing Lan²

Affiliations

¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: bblechter@jhu.edu.
² Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³ Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
⁴ Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
⁵ Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China.
⁶ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
⁷ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA; Department of Statistics, Sookmyung Women's University, Seoul, Republic of Korea.
⁸ 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.
⁹ 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.
¹⁰ Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
¹¹ Genomic Research Center, Academia Sinica, Taipei, Taiwan.
¹² 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.
¹³ Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
¹⁴ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹⁵ Department of Internal Medicine, E-Da Cancer Hospital, School of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹⁶ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹⁷ Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
¹⁸ National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
¹⁹ Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
²⁰ Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
²¹ Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
²² Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
²³ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
²⁴ 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.
²⁵ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China.
²⁶ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁷ 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.
²⁸ 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.
²⁹ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
³⁰ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
³¹ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
³² Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
³³ Department of Pathology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
³⁴ 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.
³⁵ Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
³⁶ 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.
³⁷ 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.
³⁸ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

PMID: 33385923
PMCID: PMC8378844
DOI: 10.1016/j.envint.2020.105975

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

Batel Blechter et al. Environ Int. 2021 Feb.

. 2021 Feb:147:105975.

doi: 10.1016/j.envint.2020.105975. Epub 2020 Dec 29.

Authors

Affiliations

¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: bblechter@jhu.edu.
² Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
³ Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
⁴ Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
⁵ Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China.
⁶ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
⁷ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA; Department of Statistics, Sookmyung Women's University, Seoul, Republic of Korea.
⁸ 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.
⁹ 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.
¹⁰ Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
¹¹ Genomic Research Center, Academia Sinica, Taipei, Taiwan.
¹² 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.
¹³ Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
¹⁴ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹⁵ Department of Internal Medicine, E-Da Cancer Hospital, School of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹⁶ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹⁷ Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
¹⁸ National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
¹⁹ Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
²⁰ Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
²¹ Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
²² Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
²³ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
²⁴ 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.
²⁵ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China.
²⁶ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁷ 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.
²⁸ 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.
²⁹ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
³⁰ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
³¹ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
³² Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
³³ Department of Pathology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
³⁴ 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.
³⁵ Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
³⁶ 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.
³⁷ 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.
³⁸ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

PMID: 33385923
PMCID: PMC8378844
DOI: 10.1016/j.envint.2020.105975

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.

Keywords: Gene-environment interaction; Household coal use; Lung adenocarcinoma; Never-smoking women in Asia; Polygenic risk score.

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Conflict of interest statement

Conflict of interest

The authors declare no competing interest.

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References

1. Barone-Adesi F, Chapman RS, Silverman DT, He X, Hu W, Vermeulen R, Ning B, Fraumeni JF, Rothman N, Lan Q, 2012. Risk of lung cancer associated with domestic use of coal in Xuanwei, China: retrospective cohort study. BMJ 345, e5414. 10.1136/BMJ.E5414 - DOI - PMC - PubMed
1. Bhattacharjee S, Chatterjee N, Han S,A, Wheeler W, 2012. CGEN: An R package for analysis of case-control studies in genetic epidemiology.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A, 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 68, 394–424. 10.3322/caac.21492 - DOI - PubMed
1. Chen W, Zheng R, Zeng H, Zhang S, 2015. Epidemiology of lung cancer in China. Thorac. cancer 6, 209–15. 10.1111/1759-7714.12169 - DOI - PMC - PubMed
1. Chen Y-H, Chatterjee N, Carroll RJ, 2009. Shrinkage Estimators for Robust and Efficient Inference in Haplotype-Based Case-Control Studies. J. Am. Stat. Assoc. 104, 220–233. 10.1198/jasa.2009.0104 - DOI - PMC - PubMed

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Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

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Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

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