Type 2 diabetes and colorectal cancer: genetic causality explored via Mendelian randomization
Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The global burden of type 2 diabetes (T2D) and colorectal cancer (CRC) continues to rise. Observational studies have suggested a link between T2D and an elevated risk of CRC. However, these studies are often susceptible to confounding factors and reverse causation, leading to inconsistent findings. There is a specific gap in knowledge regarding the causal nature of the relationship between T2D and CRC, which this study aims to address using a more robust approach. To fill this gap, we employed Mendelian randomization (MR), a method that uses genetic variants as instrumental variables (IVs) to infer causality, providing clearer insight into the genetic links between T2D and CRC. METHODS: A bidirectional MR study was conducted to investigate the causal links between T2D and CRC. Genetic instruments for T2D were derived from two large genome-wide association studies (GWAS) with a total sample size of X individuals, and CRC genetic instruments were obtained from a GWAS with Y individuals. The MR analysis utilized the inverse-variance weighted (IVW) method as the primary analysis, alongside sensitivity analyses such as heterogeneity and pleiotropy analysis to account for potential pleiotropy and bias. Additionally, to enhance the robustness of the findings and minimize the influence of data from different GWAS sources, we performed a meta-analysis of the IVW results. RESULTS: = 1.02, 95% CI 0.96-1.09, P = 0.469). Sensitivity analyses supported the robustness of these findings, indicating no evidence of heterogeneity or pleiotropic effects that could bias the results (all P > 0.05). CONCLUSION: Our bidirectional MR study and meta-analysis provide evidence that T2D increases the risk of colorectal cancer. However, there is no evidence to support a reverse causal relationship. These findings highlight the importance of monitoring and managing T2D as part of CRC prevention strategies.
Source: Discover Oncology
Authors: Qiuhong Ke, Yongbing Huang, Libin Cheng, Chaolin Lin, Linhua Zhao, Wulong Huang, Zhisheng Chen, Yimin Xu, Yipiao Huang, Lanlan Cai, Bin Lin, Rui Tang
Institution: Southwest Medical University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,590
Funder: Putian University
OpenAlex ID: W4404796491