ObjectiveTo identify causal effects and potential mechanisms of oxidative stress (OS) genes in lung cancer. MethodsOS-related genes were extracted from the GeneCards database. Integration analysis of genome-wide association study (GWAS) data for lung cancer with gene expression and DNA methylation quantitative trait loci (eQTL and mQTL) in blood was performed using the summary data-based Mendelian randomization (SMR) approach to determine the causal relationship between OS genes and lung cancer risk. Colocalization analysis of OS gene QTLs and lung cancer risk loci was performed to gain insight into the potential regulatory mechanisms of lung cancer risk. ResultsA potential causal relationship between OS-related genes and lung cancer was identified by SMR analysis. AGER expression level was found to be associated with lung cancer risk [OR=1.944, 95%CI (1.431, 2.640), P<0.001], and ATF6B expression level was associated with lung cancer risk [OR=1.508, 95%CI (1.287, 1.767), P<0.001]. Meanwhile, ATF6B methylation level was associated with lung cancer risk. ConclusionOS-related genes are associated with lung cancer, which may be a potential site of action for anti-cancer drugs.
ObjectiveTo explore whether there is a causal relationship between intestinal flora and esophageal cancer. MethodsSummary statistics of intestinal flora and esophageal cancer were obtained from the genome-wide association studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. ResultsIn the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.001), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter[OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. ConclusionOxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.
Objective To analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the IEU database, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratios (OR), and sensitivity analyses were performed to ensure the accuracy of the results. ResultsNeuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.