Summary
This Mendelian randomisation study assessed causal relationships between 486 genetically-predicted blood metabolites and colorectal cancer risk using European GWAS data. Six metabolites showed significant associations with colorectal cancer, with three (pyruvate, 1-linoleoylglycerophosphoethanolamine, and gamma-glutamylthreonine) demonstrating independent direct effects. The findings provide genetic evidence supporting metabolic pathways relevant to colorectal cancer aetiology, though direct dietary or farming system implications require further investigation.
UK applicability
These findings identify metabolic biomarkers potentially relevant to colorectal cancer prevention in European populations, including the UK. However, the study is based on genetic associations rather than dietary interventions or food production systems, so application to UK farming or nutritional policy would require translation through additional observational and experimental evidence linking specific foods or agricultural practices to these metabolite levels.
Key measures
Odds ratios and 95% confidence intervals for metabolite–colorectal cancer associations; statistical significance assessed via inverse variance weighted analysis with complementary MR-Egger and weighted median methods; sensitivity analyses including Cochran Q test, MR-Egger intercept test, MR-PRESSO, Radial MR, and leave-one-out analysis
Outcomes reported
The study identified six blood metabolites with causal associations to colorectal cancer risk using Mendelian randomisation, including pyruvate, 1,6-anhydroglucose, nonadecanoate, 1-linoleoylglycerophosphoethanolamine, 2-hydroxystearate, and gamma-glutamylthreonine. Multivariable analysis determined which metabolites exert direct independent effects on colorectal cancer.
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