Exploring the genetic link between type 2 diabetes and its complications and esophageal malignancy: A Mendelian randomization study

Type 2 diabetes (T2D) is an important risk factor for a range of GI malignancies. Nevertheless, the causal relationship between T2D and esophageal malignancies remains to be elucidated. Furthermore, the mechanisms leading to progression from T2D to esophageal malignancy have not been clearly characterized. The purpose of this study was to conduct a Mendelian randomization (MR) study to investigate the causal effect of T2D and its complications on the development of esophageal malignancies. In addition, this study aimed to perform a multivariate MR analysis to exclude potential confounders in this association. Genetic variation was used as an instrumental variable for T2D. Pooled data on T2D, as well as on T2D with complications and esophageal malignancies, were obtained from the European Bioinformatics Institute and Finnish databases. The study was conducted using 2-sample MR, multivariate MR. The study revealed a causal relationship between T2D (N = 4,90,089), T2D with comorbidities and esophageal malignancies (N = 1,74,238; T2D: odds ratio = 1.36, 95% confidence interval: 1.07–1.72, P = .01). Even after adjusting for confounders such as body mass index and hypertension, T2D remained statistically significant (odds ratio = 1.31, 95% confidence interval: 1.02–1.69, P = .036). The present MR study supports T2D as a causal risk factor for esophageal malignancy. Further research is warranted to investigate whether other lifestyle factors (such as diet and physical activity) have a causal role in esophageal malignancy.