Human blood metabolites and the risk of colorectal cancer: A Mendelian randomization study
Abstract
Background: Metabolomics can offer vital information into a cancer’s condition. Despite its potential, research on the metabolites linked to colorectal cancer (CRC) remains limited. From a cell molecular biomechanics perspective, understanding these metabolite associations can offer a deeper understanding of the disease’s underlying mechanisms. We performed Mendelian randomisation (MR) analyses to investigate causal associations between 486 blood metabolites and CRC. Methods: Data on blood metabolites were derived from a Genome-wide association study (GWAS) involving 7824 Europeans. Additionally, summary statistics for CRC were sourced from the FinnGen consortium database. To explore the causal relationship between CRC and blood metabolites, we primarily utilized the inverse variance weighted (IVW) analysis. Supplementary analyses incorporated MR-Egger and weighted median methods to ensure the robustness of our findings. The potential for pleiotropic effects was evaluated using the Cochran’s Q test and the MR-Egger intercept test. Furthermore, colocalization analyses were performed to ascertain whether the observed associations were influenced by specific genetic loci within the genomic region. Results: The results of this study indicated significant associations between eight metabolites: Indolelactate (OR = 2.62, 95% confidence interval (CI): 0.26–1.66, p = 0.007), 1-heptadecanoylglycerophosphocholine (OR = 1.37, 95% CI: 0.10–0.54, p = 0.005), 1-stearoylglycerophosphocholine (OR = 3.47, 95% CI: 0.65–1.84, p = 0.00005) , X-11792 (OR = 0.57, 95% CI: −0.94–−0.17, p = 0.005), X-12038 (OR = 0.44, 95% CI: −1.50–−0. 12, p = 0.021), X-12212 (OR = 1.96, 95% CI: 0.10–1.25, p = 0. 022), X-14056 (OR = 0.50, 95% CI: −1.28–−0.12, p = 0.018) , X-14745 (OR 0.41, 95% CI: −1.48–−0.31, p = 0.003) and CRC. These metabolites might play roles in altering the mechanical properties of cells in the colon. They could potentially affect the cytoskeletal structure, cell membrane fluidity, or the way cells interact with the extracellular matrix. Conclusion: The eight identified blood metabolites with causative influence on CRC provide valuable clues for understanding CRC from a cell molecular biomechanics angle, which can further aid in its screening, prevention, and treatment strategies.
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