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

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.

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.

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.

Our study indicated that metabolic syndrome increases the risk of CRC, particularly in patients with abdominal obesity.