Association between type 2 diabetes mellitus and gastric cancer: A Mendelian randomization study

Background & aims: Type 2 diabetes mellitus (T2DM) has been proven to be associated with the risk of developing gastric cancer (GC) in observational studies. However, the result was affected by many potential confounding factors, so a Mendelian randomization (MR) study was conducted to assess the association. Method We performed bidirectional MR analyses to explore the causal relationship between T2DM and GC, as well as the risk factors for GC. To examine the effect caused by confounding factors, we took part of the risk factors into research. We also conducted a meta-analysis of the results from different data sources. Result The MR analysis revealed a negative correlation between T2DM and GC (odds ratio = 0.10, 95% confidence interval, 0.01–0.69; P  = .02). Regarding the relationship between risk factors for GC and T2DM, we found that BMI (OR, 1.04; 95% CI, 1.04–1.05; P  < .001), physical activity (OR, 0.98; 95% CI, 0.97-1.00; P  = .01), ever smoking (OR, 1.03; 95% CI, 1.01–1.06; P  < .001) and alcohol consumption (OR, 1.01; 95% CI, 1.00-1.02; P  = .01) could increase the occurrence of T2DM. On the other hand, T2DM could increase the rate of HP infection (OR, 2.06; 95% CI, 1.16–3.66; P  = .01) and EBV infection (OR, 6.31; 95% CI, 1.12–35.64; P  = .04) to affect the development of GC. These factors could affect the outcome of observational studies, which differed from our research. Conclusion The results showed that T2DM had a negative correlation with GC. Confounding factors, including high BMI, physical activity, smoking, alcohol consumption, HP infection, and EBV infection, could reverse the tendency. Further research should be conducted to explore the specific mechanism regarding the causality between the two diseases.