Metabolic syndrome and risk of colorectal cancer: A Mendelian randomization study

Heliyon. 2023 Dec 19;10(1):e23872. doi: 10.1016/j.heliyon.2023.e23872. eCollection 2024 Jan 15.

Abstract

Background: Observational studies have previously demonstrated a significant relationship among both metabolic syndrome (Mets) and colorectal cancer (CRC). Whether there is a causal link remains controversial.

Objective: To clarify whether Mets and their components have a causal effect on colorectal cancer, we have carried out a bidirectional Mendelian randomization analysis (MR).

Methods: This study started from genome-wide association data for Mets and its 5 components (hypertension, waist circumference, fasting blood glucose, serum triglycerides, and serum high-density lipoprotein cholesterol) and colorectal cancer. Mendelian randomization (MR) techniques were used in the study to examine their associations.

Results: After Benjamini-Hochberg multiple corrections, genetically predicted significant causal link exists between WC (waist circumference) and CRC. The OR was 1.35 (95 % CI: 1.08-1.69; p = 0.0096). Other Mets components (HBP, FBG, TG, HDL), on the other hand, found no evidence of a genetic link between CRC and Mets. In addition, MR results showed that CRC was not causally related to either Mets or the components. We get the same result in the validated dataset.

Conclusion: According to the bidirectional MR investigation shows a significant causal relationship among obesity and CRC in the Mets component but no causal relationship in the opposite direction.

Keywords: Colorectal cancer (CRC); Instrumental variant (IV); Mendelian randomization (MR); Metabolic syndrome (mets); Single-nucleotide polymorphism (SNP); Waist circumference (WC).