Causal Relationship Found Between Obesity in Metabolic Syndrome and CRC

A study published in Heliyon determined through Mendelian randomization that obesity related to metabolic syndrome (MetS) had a causal relationship with colorectal cancer (CRC).

CRC is the fourth deadliest cancer in the world, and knowing which underlying factors can lead to CRC is important to making sure that all people get the care they need in a timely manner. MetS is a possible risk factor for CRC, but the full relationship has not been explored. This study aimed to use Mendelian randomization to evaluate the relationship between MetS and all of its components and CRC in both directions.

The most representative genome-wide association studies (GWAS) were used for their statistics on MetS, hypertension, waist circumference, serum triglycerides, fasting blood glucose, and serum high-density lipoprotein cholesterol (HDL-C). Genetic data for all 5 of the aspects of MetS were implemented into the Mendelian randomization. Participants were restricted to those of mostly European origin. Single-nucleotide polymorphisms (SNPs) were also analyzed for exposure factors. Summary-level data for MetS were taken from the UK Biobank. The FinnGen cohort was used for CRC summary-level data.

Doctor presenting image of lower intestine | Image credit: mi_viri - stock.adobe.com

There were 87 SNPs included for MetS, 46 for waist circumference, 170 for high blood pressure, 75 for fasting blood glucose, 72 for serum triglycerides, and 116 for HDL-C included in the Mendelian randomization. Waist circumference was found to be significantly associated with increased risk of CRC (OR, 1.35; 95% CI, 1.08-1.69). The other components showed no significant association with CRC. A validation analysis continued to find that waist circumference and CRC were associated (OR, 1.002; 95% CI, 1.0002-1.0041) but the other components showed no sign of an association.

The reverse analysis used 8 variants of SNP for MetS, 2 for waist circumference, 5 for high blood pressure, 5 for fasting blood glucose, 2 for serum triglycerides, and 2 for HDL-C. The reverse analysis found that there was no causal relation from CRC to MetS or the other components. There was no heterogeneity in this analysis.

There were some limitations to this study. How genetic tools work and how they affect the risk factors of CRC are unclear. Covariates, such as sex, smoking, alcohol consumption, and underlying diseases, could not be stratified for in the pooled data for CRC, which left it unclear if MetS could promote the risk of CRC in some subgroups.

The researchers concluded that waist circumference had a causal relationship to CRC, which also strengthens the reasoning for the previously established relationship between CRC and MetS. The researchers concluded by saying it was “imperative to prioritize certain aspects in early cancer screening, such as directing CRC screening efforts toward obese individuals and promoting weight loss among this population to mitigate CRC risk.”

Reference

Chen Y, Kong W, Liu M, et al. Metabolic syndrome and risk of colorectal cancer: a Mendelian randomization study. Heliyon. Published online December 19, 2023. doi:10.1016/j.heliyon.2023.e23872