Association between type 2 diabetes and gastric cancer in Europeans and East Asians based on two sample Mendelian randomization.

BACKGROUND

There are conflicting results and potential methodological flaws of previous observational studies on the association between T2DM and the risk of gastric cancer.This two-sample Mendelian randomization (MR) study aimed to investigate the causal association between type 2 diabetes mellitus (T2DM) and gastric cancer in different ethnic populations.

METHODS

Exposure variables were obtained from genome-wide association studies (GWAS) of T2DM in European population (finn-b-E4_DM2; 32,469) and East Asian population (ebi-a-GCST90018706; n = 45,383). Concomitantly, we utilized summary-level genetic data for gastric cancer in Europeans population (ebi-a-GCST90018849; n = 1029) and East Asians population (ebi-a-GCST90018629; n = 7,921) as the outcome measure. Causal associations between T2DM and gastric cancer in the same ethnic groups were primarily determined using the inverse-variance weighted (IVW) method.

RESULTS

A total of 62 and 106 single nucleotide polymorphisms associated with T2DM were selected for in Europeans and East Asians, respectively. The IVW analysis indicated that there was a significant inverse association between T2DM and gastric cancer in Europeans (odds ratio [OR] 0.917; 95% confidence interval [CI] 0.855-0.984) and East Asians (OR 0.881; 95% CI 0.845-0.918). The weighted median and Weighted mode regression models produced similar results. MR-Egger regression analysis suggested the absence of horizontal pleiotropy. The leave-out sensitivity analysis demonstrated that the results were stable.

CONCLUSION

This MR study revealed that T2DM may be associated with a reduced risk of gastric cancer in European and East Asian population.