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. 2024 Sep 30;13(9):4938-4956.
doi: 10.21037/tcr-24-359. Epub 2024 Sep 9.

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

Jili Zhang #  1   2 , Zhibin Hao #  3 , Zewei Chen #  4 , Xingxing Su  5 , Wentao Xu  6 , Xin Jiang  2 , Xinwen Nian  1
Affiliations

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

Jili Zhang et al. Transl Cancer Res. .

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.

Keywords: Mendelian randomization (MR); cancer detection; metabolism; pan-cancer; plasma metabolites.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-359/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The study design. Flowchart of the study. GWAS, genome-wide association study; IVs, instrumental variables; MR, Mendelian randomization; LD, linkage disequilibrium.
Figure 2
Figure 2
Significant MR results of causal effects between plasma metabolites and cancer risk. N.SNP, the number of SNPs used as IVs; SNP, single-nucleotide polymorphism; IVs, instrumental variables; IVW, inverse variance-weighted; FDR, false discovery rate; OR, odds ratio; CI, confidence interval; MR, mendelian randomization; GPC, glycerylphosphorylcholine; GPG, glycerophosphoethanolamine; GPE, glycero-3-phosphorylglycerol.
Figure 3
Figure 3
Significant results of reverse MR. (A) MR results of causal effects between lung cancer risk and 1-palmitoyl-2-linoleoyl-GPC (16:0/18:2) levels. (B) Scatter plots of causality, the slope of each line corresponding to the estimated MR effect in different models. (C) Forest plot with the estimated MR effect of each IV in IVW and MR-Egger models. (D) Leave one out of sensitivity tests. Calculate the MR results of the remaining IVs after removing the IVs one by one. (E) Funnel plot from genetically predicted 1-palmitoyl-2-linoleoyl-GPC (16:0/18:2) levels on lung cancer. N.NSP, the number of SNPs used as IVs; SNP, single-nucleotide polymorphism; IVs, instrumental variables; FDR, false discovery rate; OR, odds ratio; CI, confidence interval; MR, Mendelian randomization; SE, standard error; GPC, glycerylphosphorylcholine.
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References

    1. Rahib L, Wehner MR, Matrisian LM, et al. Estimated Projection of US Cancer Incidence and Death to 2040. JAMA Netw Open 2021;4:e214708. 10.1001/jamanetworkopen.2021.4708 - DOI - PMC - PubMed
    1. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin 2023;73:17-48. 10.3322/caac.21763 - DOI - PubMed
    1. Heron M. Deaths: Leading Causes for 2017. Natl Vital Stat Rep 2019;68:1-77. - PubMed
    1. Fitzgerald RC, Antoniou AC, Fruk L, et al. The future of early cancer detection. Nat Med 2022;28:666-77. 10.1038/s41591-022-01746-x - DOI - PubMed
    1. Singh AK, McGuirk JP. CAR T cells: continuation in a revolution of immunotherapy. Lancet Oncol 2020;21:e168-78. 10.1016/S1470-2045(19)30823-X - DOI - PubMed

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