Key result
Genetically predicted phosphatidylcholine 18:1_20:2 is linked to ~10% lower CRC risk.
Why the study?
Lipid metabolism plays a key role in colorectal cancer, but the causal links between genetically determined lipids and colorectal cancer needed assessment to identify potential lipid markers and treatment targets.
Do genetically determined levels of specific lipids affect the risk of colorectal cancer?
Meta-Analysis
Do genetically determined levels of specific lipids affect the risk of colorectal cancer?
Odds Ratio: 0.9048 (95% CI 0.8829–0.9272)
p-value: p=1.6694 × 10−13
Genetically predicted levels of specific phosphatidylcholines are causally associated with colorectal cancer risk, suggesting potential lipid markers and treatment targets.
May inform future CRC biomarker research; hypothesis-generating and should not yet change clinical prevention or screening.
Background: Lipid metabolism plays a key role in colorectal cancer (CRC). Our two-sample Mendelian randomization (MR) analysis assessed the causal links between 179 genetically determined lipids and CRC to find potential lipid markers and treatment targets. Methods: Data on 179 lipids were gathered from public genome-wide association studies (GWAS) databases. Genetic associations with CRC were sourced from FinnGen and the GWAS Catalog. MR analysis was conducted for each lipid, followed by inverse variance weighting meta-analysis. Results: Elevated levels of genetically predicted phosphatidylcholine (PC; 18:1_20:2) were associated with a reduced risk of CRC, with a meta-analysis odds ratio (OR) of 0.9048 (95% CI: 0.8829–0.9272, P = 1.6694 × 10−13). Conversely, increased levels of genetically predicted PC (O-16:1_20:4) were associated with an elevated CRC risk, with a meta-analysis OR of 1.1025 (95% CI: 1.0748–1.13085, P = 7.3163 × 10−12). Reverse causality was ruled out. Conclusion: Our findings provide evidence for the causal relationship between these two lipids and CRC risk, offering new insights into the prevention and pathogenesis of CRC.
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Ran et al. (2024) conducted a meta-analysis in colorectal cancer (CRC). Genetically determined lipids was evaluated on colorectal cancer (CRC) risk (OR 0.9048, 95% CI 0.8829-0.9272, p=1.6694 × 10−13). Genetically predicted phosphatidylcholine (18:1_20:2) was associated with reduced CRC risk (OR 0.9048), while PC (O-16:1_20:4) was associated with increased risk (OR 1.1025).
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