Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia. (February 2021)

• Record Type: Journal Article
• Authors: Blechter, Batel; Wong, Jason Y.Y.; Agnes Hsiung, Chao; 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, Maria; 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; Jie Seow, Wei; 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, Maria; 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;
• Is Part Of: Environment international. Volume 147(2021)
• Publication Date: 2021-02
• Subjects: Lung adenocarcinoma -- Polygenic risk score -- Gene-environment interaction -- Household coal use -- Never-smoking women in Asia; GWAS genome-wide association study -- FLCCA Female Lung Cancer Consortium in Asia -- PRS polygenic risk score -- OR odds ratio -- CI confidence interval -- NCI National Cancer Institute -- GELAC Genetic Epidemiological Study of Lung Adenocarcinoma -- SLCS Shenyang Lung Cancer Study -- SWHS Shanghai Women's Health Study -- SNP single nucleotide polymorphism -- RERI relative excess risk due to interaction -- EB Empirical Bayes -- IARC International Agency for Research on Cancer -- PAH polycyclic aromatic hydrocarbons -- PM particulate matter; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2020.105975
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: The interaction between coal use and cumulative genetic susceptibility to lung cancer is unclear. We found weaker genetic susceptibility to lung adenocarcinoma among coal users who never smoked. Lung cancer pathogenesis may differ depending on exposure to coal combustion products. 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.