| Title: | Blood metabolic biomarkers and colorectal cancer risk: results from large prospective cohort and Mendelian randomisation analyses |
| Journal: | British Journal of Cancer |
| Published: | 30 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40307439/ |
| DOI: | https://doi.org/10.1038/s41416-025-02997-4 |
| URL: | https://www.nature.com/articles/s41416-025-02997-4.pdf |
Publication 15439
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Abstract
BackgroundEmerging evidence suggests metabolic dysregulation may contribute to colorectal cancer (CRC) aetiology. We aimed to identify pre-diagnostic metabolic biomarkers for CRC risk in 230,420 UK Biobank participants.MethodsNuclear magnetic resonance spectroscopy was used to quantify 249 metabolic biomarkers in plasma samples collected at baseline. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CIs) for associations of metabolic biomarkers with CRC risk after adjusting for potential confounders. To infer the potential causality of biomarkers that were associated with CRC independent of the others, we performed genome-wide association analyses among 199,732 UK Biobank participants of European ancestry to identify biomarker-associated genetic variants, followed by two-sample Mendelian randomization (MR) analyses using summary statistics of 78,473 CRC cases and 107,143 controls of European ancestry.ResultsDuring a median follow-up time of 9.7 years, 2,410 incident primary CRC cases were identified. Among 43 CRC-associated (P-value < 0.001) metabolic biomarkers, ten biomarkers including fatty acids (FAs), inflammation, ketone bodies, and lipoprotein lipids were associated with CRC risk after mutual adjustment. MR analyses provided strong evidence for potential causal associations of CRC risk with percentages of linolic acid [odds ratio (OR) = 0.89, 95% CI = 0.83-0.96, P-value = 3 × 10-3] and saturated FAs (OR = 1.14, 95% CI = 1.03-1.25, P-value = 9 × 10-3) to total FAs.ConclusionsWe identified multiple CRC-associated metabolic biomarkers. Perturbed lipid and lipoprotein metabolism may promote colorectal carcinogenesis.</p>
13 Keywords
- Aged
- Biomarkers, Tumor
- Colorectal Neoplasms
- Female
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
- Prospective Studies
- Risk Factors
- United Kingdom
10 Authors
- Fangcheng Yuan
- Guochong Jia
- Wanqing Wen
- Shuai Xu
- Valerie Gunchick
- Kui Deng
- Jirong Long
- Danxia Yu
- Xiao-Ou Shu
- Wei Zheng
1 Application
| Application ID | Title |
|---|---|
| 55411 | Metabolomic profiling in relation to risks of cancer of the colon, rectum, pancreas, liver and biliary tract |
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