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

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. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

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. Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia. Environment international. 2021 Feb;147:105975

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PMID: 33385923

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