Causal Relationship Between Metabolic Traits and Risk of NSCLC: A Two-Sample Mendelian Randomization Analysis
Year: 2025
Type: article
Study design: Observational Study
Abstract: Although the impact of circulating metabolites on the immune microenvironment of lung cancer has been recognized, the causal relationship between these metabolites and non-small cell lung cancer (NSCLC) remains unclear.We investigated whether 233 metabolic traits have a causal effect on NSCLC using data from population-based genome-wide association studies (GWAS).We employed the inverse variance weighted (IVW) method with random effects as the primary analytical tool.After performing two-sample Mendelian randomization (MR) analysis of 233 metabolic traits on NSCLC risk, we selected the significant ones for further sensitivity analyses.Applying a false discovery rate (FDR) correction (PFDR < 0.05), we identified a causal relationship between two metabolic traits and NSCLC: the ratio of Omega-3 fatty acids to total fatty acids (Omega_3_pct) (OR: 1.18, 95% CI: 1.08-1.29,PFDR=0.036) and the ratio of 22:6 docosahexaenoic acid to total fatty acids (DHA_pct) (OR: 1.26, 95% CI: 1.11-1.42,PFDR=0.036).Sensitivity analyses yielded consistent results.We innovatively utilized GWAS data for multiple metabolic traits to conduct a two-sample Mendelian randomization analysis of the association between 233 metabolic traits and NSCLC.The findings suggest that higher proportions of Omega-3 fatty acids and 22:6 docosahexaenoic acid in total fatty acids may causally increase the risk of NSCLC, providing novel insights into the role of circulating metabolites in lung cancer development.
Source: Journal of Cancer
DOI: 10.7150/jca.109913
Authors: Xin Li, Weifang Cui, Chaojun Duan, Chunfang Zhang
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,337
OpenAlex ID: W4414708280