Causality between insulin use and malignant tumors of the digestive system: a two-sample Mendelian randomized study

Abstract

Background According to the results of the available cohort studies, there is no association between insulin use and digestive system cancers. But a number of meta-analyses have shown that insulin use increases the risk of digestive system tumors. Therefore, the causal relationship between the two needs to be further determined. We used two-sample Mendelian randomization (MR) to explore the causal association between insulin use and digestive system cancers. Methods The analysis was performed by selecting SNPs that were strongly associated with insulin use as instrumental variables in a genome-wide association study (GWAS) and using aggregated statistics on digestive system neoplasm as the end event. Inverse variance weighting (IVW) is used as the main analysis method in this study, and weighted median, MR-Egger regression, weighted mode and simple mode were used as supplementary methods to the results. Finally, the reliability of this study is evaluated through heterogeneity test, pleotropy analysis and sensitivity analysis. Result A total of eight SNPs associated with insulin use were included as IVs, and random-effects IVW analysis showed that insulin use was associated with an increased risk of CRC (OR = 1.1037, 95%CI = 1.0183–1.1962, P = 0.016). There was no statistically significant association between insulin use and the development of other digestive system tumors. The results were not affected by pleiotropy and heterogeneity, and the reliability of the results was confirmed by sensitivity analysis. Conclusion Our Mendelian randomization study showed that insulin use was associated with an increased risk of CRC, while there was no clear association with other digestive system tumors, however, further Mendelian randomization studies with larger sample sizes of GWAS data are needed to verify this relationship.