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 HsiaoYing 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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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 × 1026). 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.

Original languageEnglish (US)
Article number105975
JournalEnvironment international
StatePublished - Feb 2021


  • Gene-environment interaction
  • Household coal use
  • Lung adenocarcinoma
  • Never-smoking women in Asia
  • Polygenic risk score

ASJC Scopus subject areas

  • Environmental Science(all)


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