| Summary: | Abstract Background Observational epidemiological studies suggest that lung cancer risk may be raised by gastroesophageal reflux disease (GERD); however, the causal relationship between them remains unknown. Our study performed the two‐sample Mendelian randomization (MR) approach to examine the causal relationship between GERD and lung cancer. Methods Instrument variables were found to be independent single nucleotide polymorphisms (SNPs) that were highly linked with GERD (n = 129,080). Summary data from genome‐wide association studies (GWAS) data were used to determine outcomes for lung cancer (n = 11,348), squamous cell lung cancer (LUSC), and lung adenocarcinoma (LUAD). In this study, three MR statistical techniques (inverse variance weighted (IVW), MR‐Egger, and weighted median) were used to examine the potential causative relationship between GERD and the risk of lung cancer. Cochran's Q test, MR‐Egger intercept test, leave‐one‐out analysis, and the funnel plot were all used in sensitivity analyses. Results The main IVW method revealed that GERD substantially increased the risk of lung cancer [odds ratio (OR) = 1.37; 95% CI 1.16–1.63, p = 0. 0003], which was also supported by weighted median and MR‐Egger analyses. Using IVW estimate, similar causal relationships were also observed between GERD and LUSC (OR = 1.56; 95% CI 1.26–1.93, p = 5.35 × 10−5) and LUAD (OR = 1.45; 95% CI 1.09–1.93, p = 0.01). Although potential heterogeneity was observed in some studies, random effect IVW was not violated by the heterogeneity, indicating that the causal effect was robust. Conclusion GERD was positively associated with the risk of lung cancer, for LUSC and LUAD. This study shed light on a new direction for prevent strategy of lung cancer and therapeutic perspectives in patients with GERD.
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