Glycemic Traits and Oesophageal Cancer a Two-Sample and Multivariable Mendelian Randomization Study

Abstract

Abstract Background: Observational studies indicate a potential link between increased blood glucose levels and the development of oesophageal cancer. However, the causal relationship between glycemic traits and oesophageal cancer has not been clarified yet. The aim of this research was to examine if there is a genetic link between glycemic characteristics and oesophageal cancer through the use of Mendelian randomization analysis. Methods: We conducted a TSMR analysis and MVMR using publicly available GWAS data on the European population. The primary analysis utilized the IVW method, which was subsequently validated through comprehensive complementary and sensitivity analyses. Results: IVW analysis revealed a substantial correlation (OR=1.612, P=0.0228) between type 2 diabetes (T2DM) and oesophageal cancer. After accounting for body mass index (BMI), this association remained to be statistically significant in multivariate MR analyses (OR=1.662, P=0.0416). There was only a small amount of evidence indicating a possible link between oesophageal cancer and other glycemic traits after excluding the outliers. Conclusions: Our study further supports the evidence that European individuals with T2DM are at an increased risk of developing oesophageal cancer. It implies that pharmacological or lifestyle treatments for individuals with T2DM could potentially be advantageous in the prevention of oesophageal tumor development.