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J1824028,M1552003Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women

Jason Y.Y. Wong; Han Zhang; Chao A. Hsiung; Kouya Shiraishi; Kai Yu; Keitaro Matsuo; Maria Pik Wong; Yun-Chul Hong; Jiucun Wang; Wei Jie Seow; Zhaoming Wang; Minsun Song; Hee Nam Kim; I-Shou Chang; Nilanjan Chatterjee; Wei Hu; Chen Wu; Tetsuya Mitsudomi; Qing Lan
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摘要

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

关键词

TuberculosisLung cancerLung adenocarcinomaMendelian randomizationPathway analysis

出版信息

论文状态
公开发表
期刊名称
Genomics
发表日期
2019-7-12
卷
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期
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页码
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DOI
10.1016/j.ygeno.2019.07.008

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