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Background Emissions from household coal combustion associated with cooking and heating are an important public health issue, particularly in China where hundreds of millions of people are exposed. Although coal emissions are a known human carcinogen, there is still uncertainty about the level of risk for lung and other cancers.Methods We performed a meta-analysis on 25 case–control studies (10 142 cases and 13 416 controls) to summarize the association between household coal use and lung cancer risk, and to explore the effect modification of this association by geographical location.Results Using random-effects models, household coal use was found to be associated with lung cancer risk among all studies throughout the world [odds ratio (OR) = 2.15; 95% confidence interval (CI) = 1.61–2.89, Nstudies = 25], and particularly among those studies carried out in mainland China and Taiwan (OR = 2.27; 95% CI = 1.65–3.12, Nstudies = 20). Stratification by regions of mainland China and Taiwan found a variation in effects across the regions, with south/southeastern (OR = 3.27; 95% CI = 1.27–8.42, Nstudies = 3) and southwestern China (OR = 2.98; 95% CI = 1.18–7.53, Nstudies = 3) experiencing the highest risk. The elevated risk associated with coal use throughout Asia was also observed when stratifying studies by gender, smoking status, sample size, design (population vs hospital case–control) and publication language. No significant publication bias was found (pBegg’s = 0.15).Conclusions Our results provide evidence that although the carcinogenic effect of coal use varies by location, coals from many locations exhibit elevated lung cancer risks. [ABSTRACT FROM AUTHOR]

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.)

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk., (Published 2014. This article is a US Government work and, as such, is in the public domain of the United States of America.)