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Title: Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia
Authors: Blechter, Batel
Wong, Jason Y. Y.
Agnes Hsiung, C.
Hosgood, H. Dean
Yin, Zhihua
Shu, Xiao-Ou
Zhang, Han
Shi, Jianxin
Song, Lei
Song, Minsun
Zheng, Wei
Wang, Zhaoming
Caporaso, Neil
Burdette, Laurie
Yeager, Meredith
Berndt, Sonja I.
Teresa Landi, M.
Chen, Chien-Jen
Chang, Gee-Chen
Hsiao, Chin-Fu
Tsai, Ying-Huang
Chen, Kuan-Yu
Huang, Ming-Shyan
Su, Wu-Chou
Chen, Yuh-Min
Chien, Li-Hsin
Chen, Chung-Hsing
Yang, Tsung-Ying
Wang, Chih-Liang
Hung, Jen-Yu
Lin, Chien-Chung
Perng, Reury-Perng
Chen, Chih-Yi
Chen, Kun-Chieh
Li, Yao-Jen
Yu, Chong-Jen
Chen, Yi-Song
Chen, Ying-Hsiang
Tsai, Fang-Yu
Seow Wei Jie 
Bassig, Bryan A.
Hu, Wei
Ji, Bu-Tian
Wu, Wei
Guan, Peng
He, Qincheng
Gao, Yu-Tang
Cai, Qiuyin
Chow, Wong-Ho
Xiang, Yong-Bing
Lin, Dongxin
Wu, Chen
Wu, Yi-Long
Shin, Min-Ho
Hong, Yun-Chul
Matsuo, Keitaro
Chen, Kexin
Pik Wong, M.
Lu, Daru
Jin, Li
Wang, Jiu-Cun
Seow, Adeline 
Wu, Tangchun
Shen, Hongbing
Fraumeni, Joseph F.
Yang, Pan-Chyr
Chang, I-Shou
Zhou, Baosen
Chanock, Stephen J.
Rothman, Nathaniel
Chatterjee, Nilanjan
Lan, Qing
Keywords: Gene-environment interaction
Household coal use
Lung adenocarcinoma
Never-smoking women in Asia
Polygenic risk score
Issue Date: 1-Feb-2021
Publisher: Elsevier Ltd
Citation: Blechter, Batel, Wong, Jason Y. Y., Agnes Hsiung, C., Hosgood, H. Dean, Yin, Zhihua, Shu, Xiao-Ou, Zhang, Han, Shi, Jianxin, Song, Lei, Song, Minsun, Zheng, Wei, Wang, Zhaoming, Caporaso, Neil, Burdette, Laurie, Yeager, Meredith, Berndt, Sonja I., Teresa Landi, M., Chen, Chien-Jen, Chang, Gee-Chen, Hsiao, Chin-Fu, Tsai, Ying-Huang, Chen, Kuan-Yu, Huang, Ming-Shyan, Su, Wu-Chou, Chen, Yuh-Min, Chien, Li-Hsin, Chen, Chung-Hsing, Yang, Tsung-Ying, Wang, Chih-Liang, Hung, Jen-Yu, Lin, Chien-Chung, Perng, Reury-Perng, Chen, Chih-Yi, Chen, Kun-Chieh, Li, Yao-Jen, Yu, Chong-Jen, Chen, Yi-Song, Chen, Ying-Hsiang, Tsai, Fang-Yu, Seow Wei Jie, Bassig, Bryan A., Hu, Wei, Ji, Bu-Tian, Wu, Wei, Guan, Peng, He, Qincheng, Gao, Yu-Tang, Cai, Qiuyin, Chow, Wong-Ho, Xiang, Yong-Bing, Lin, Dongxin, Wu, Chen, Wu, Yi-Long, Shin, Min-Ho, Hong, Yun-Chul, Matsuo, Keitaro, Chen, Kexin, Pik Wong, M., Lu, Daru, Jin, Li, Wang, Jiu-Cun, Seow, Adeline, Wu, Tangchun, Shen, Hongbing, Fraumeni, Joseph F., Yang, Pan-Chyr, Chang, I-Shou, Zhou, Baosen, Chanock, Stephen J., Rothman, Nathaniel, Chatterjee, Nilanjan, Lan, Qing (2021-02-01). Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia. Environment International 147 : 105975. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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. © 2020 The Authors
Source Title: Environment International
ISSN: 0160-4120
DOI: 10.1016/j.envint.2020.105975
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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