Metabolic syndrome and risk of colorectal cancer: A Mendelian randomization study.
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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.
SUBMITTER: Chen Y
PROVIDER: S-EPMC10784169 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Publications
Metabolic syndrome and risk of colorectal cancer: A Mendelian randomization study.
Chen Yuhua Y Kong Wanru W Liu Min M Li Qiang Q Wang Yuping Y Zheng Ya Y Zhou Yongning Y
Heliyon 20231219 1
<h4>Background</h4>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.<h4>Objective</h4>To clarify whether Mets and their components have a causal effect on colorectal cancer, we have carried out a bidirectional Mendelian randomization analysis (MR).<h4>Methods</h4>This study started from genome-wide association data for Mets and its 5 components (hype ...[more]
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Project description:BackgroundRecognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival.MethodsTo investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years.ResultsThe GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk.ConclusionsThese analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development.FundingThis work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used the computational facilities of the Advanced Computing Research Centre, University of Bristol - http://www.bristol.ac.uk/acrc/.
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