Dongsheng Wu, Jian Zhou, Lujia Song, Quan Zheng, Tengyong Wang, Zhizhen Ren, Yuchen Huang, Shuqiao Liu, Lunxu Liu
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引用次数: 0
Abstract
Background: Observational studies have revealed a potential association between gastroesophageal reflux disease (GERD) and lung cancer (LC), but the genetic role in their comorbidity have not been fully elucidated. This study aimed to comprehensively dissect the genetic link underlying GERD and LC.
Methods: Using large-scale genome-wide association study (GWAS) data, we investigated shared genetic architecture between GERD and LC. Our analyses encompassed genetic correlation, cross-trait meta-analysis, transcriptome-wide association studies (TWASs), and the evaluation of the causality though a bidirectional Mendelian randomization (MR) analysis with sufficient sensitivities.
Results: We identified a significant genome-wide genetic correlation between GERD and overall LC (rg =0.33, P=1.58×10-14), as well as across other subtype-specific LC (rg ranging from 0.19 to 0.39). After separating the whole genome into approximately 2,353 independent regions, 5 specific regions demonstrated significant local genetic correlation, with most significant region located at 9q33.3. Cross-trait meta-analysis revealed 22 pleiotropic loci between GERD and LC, including 3 novel loci (rs537160, rs10156445, and rs17391694). TWASs discovered a total of 49 genes shared in multiple tissues, such as lung tissues, esophagus muscularis, esophagus mucosa, and esophagus gastroesophageal junction. MR analysis suggested a significantly causal relationship between GERD and overall LC [odds ratio (OR) =1.34, 95% confidence interval (CI): 1.19-1.51], as well as other subtype-specific LC (OR ranging from 1.25 to 1.76). No evidence supports a significant causal effect of LC on GERD.
Conclusions: Our findings suggest intrinsic genetic correlation underlying GERD and LC, which provides valuable insights for screening and management of LC in individuals with GERD.
期刊介绍：
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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