Genetic prediction of the relationship between metabolic syndrome and colorectal cancer risk: a Mendelian randomization study

Abstract

Background: Despite a growing body of observational studies indicating a potential link between metabolic syndrome and colorectal cancer, a definitive causal relationship has yet to be established. This study aimed to elucidate the causal relationship between metabolic syndrome and colorectal cancer through Mendelian randomization. Methods: We screened for instrumental variables associated with metabolic syndrome and its diagnostic components and with colorectal cancer through the use of a genome-wide association study database, and conducted a preliminary Mendelian randomization analysis. To corroborate the dependability of our conclusions, an additional dataset was used for replication analysis in a Mendelian randomization method, which was further integrated with a meta-analysis. Results: Preliminary analysis using the inverse variance weighted method revealed positive correlations between metabolic syndrome (OR [95% CI] = 1.37[1.15–1.63], P = 5.02 × 10–4) and waist circumference (OR [95% CI] = 1.39[1.21–1.61], P = 7.38 × 10–6) and the risk of colorectal cancer. Replication analysis also revealed the same results: metabolic syndrome (OR [95% CI] = 1.24[1.02–1.51], P = 0.030) and waist circumference (OR [95% CI] = 1.23[1.05–1.45], P = 0.013). The meta-analysis results further confirmed the associations between metabolic syndrome (OR [95% CI] = 1.31[1.15–1.49], P < 0.001) and waist circumference (OR [95% CI] = 1.32[1.18–1.47], P < 0.001) and colorectal cancer. Conclusion: Our study indicated that metabolic syndrome increases the risk of CRC, particularly in patients with abdominal obesity.