Unveiling the atlas of associations between 1,400 plasma metabolites and 24 tumors: Mendelian randomization analyses.

Abstract

Background: Association between plasma metabolites and pan-cancer remains controversial. Herein, we performed a two-sample Mendelian randomization (MR) analysis to verify whether there is a causal relationship between the two and to point the way for cancer metabolism research.

Methods: In our research, we downloaded 1,400 plasma metabolites from a large genome-wide association study (GWAS). We also obtained GWAS summary statistics for 24 types of cancers from the publicly available GWAS database, totaling 5,003,410 European individuals. We mainly used the fixed/random-effects inverse variance-weighted (IVW) method for two-sample MR analysis.

Results: In a combined sample of 291,202 cancer cases and 4,712,208 controls, a total of 55 plasma metabolites were identified as causally associated with nine types of cancer as a result of our MR analysis [P<0.05, false discovery rate (FDR) <0.2], including methionine sulfone, gamma-glutamylcitrulline, alliin, tetradecanedioate, hexadecanedioate, glutarate, ceramide, linolenoylcarnitine, hydroxypalmitoyl sphingomyelin, 1-palmitoyl-2-linoleoyl-glycerylphosphorylcholine (1-palmitoyl-2-linoleoyl-GPC), 3-acetylphenol sulfate, retinol (vitamin a) to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) ratio, etc. Reverse MR analysis revealed a causal relationship between lung cancer and the only plasma metabolite, 1-palmitoyl-2-linoleoyl-GPC (P<0.05, FDR <0.2).

Conclusions: Our study provides a comprehensive atlas of cancer-related plasma metabolites, offering possible targets for cancer detection, as well as a reference for future research on tumorigenesis mechanisms and therapeutic targets.