Deciphering the lipid–cancer nexus: comprehensive Mendelian randomization analysis of the associations between lipid profiles and digestive system cancer susceptibility

Q: What problem does the study address about lipidomics and digestive system cancers?

It addresses uncertainty about whether specific lipid profiles causally influence the risk of digestive system cancers, rather than showing only correlation.

Q: Which cancers and lipidomic traits are examined using Mendelian randomization?

The analysis covers stomach, liver, esophageal, pancreatic, and colorectal cancers and evaluates causal effects of multiple lipidomic traits derived from public genetic databases.

Q: What key causal associations were reported in the results?

Higher sphingomyelin (d40:1) related to lower gastric cancer risk, while phosphatidylcholine (16:1_20:4) related to higher esophageal cancer risk; phosphatidylcholine (18:2_0:0) showed protection against colorectal cancer.

Sep 21, 2026

Uploaded by Violet

Digestive system cancers pose a major global health burden influenced by demographic and lifestyle shifts. Lipidomics has highlighted altered lipid metabolism in cancer biology, yet the causal links between specific lipid profiles and digestive system cancer susceptibility remain unclear. This study applies two-sample Mendelian randomization using public GWAS data to evaluate causal associations between lipidomic traits and five digestive cancer types, with IVW and sensitivity, plus reverse MR for robustness.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Jin et al. Lipids in Health and Disease (2024) 23:202 Lipids in Health and Disease [https://doi.org/10.1186/s12944-024-02191-0](https://doi.org/10.1186/s12944-024-02191-0) RESEARCH Open Access Deciphering the lipid–cancer nexus: comprehensive Mendelian randomization analysis of the associations between lipid profiles and digestive system cancer susceptibility Yongyan Jin 1, Haiyan Zhou 1, Xiaoli Jin2 and Jun Wang2* Abstract Background Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged as a pivotal area in cancer research, suggesting that alterations in lipid metabolism are closely linked to cancer development. However, the causal relationship between specific lipid profiles and digestive system cancer risk remains unclear. Methods Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results. Results Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0 . 68, P < 0. 001), while elevated levels of phosphatidylcholine (16:1_ 20:4) increased the risk of developing esophageal cancer (OR = 1 . 31, P = 0 . 02) . Conversely, phosphatidylcholine (18:2_ 0:0) had a protective effect against colorectal cancer (OR = 0 . 86, P = 0 . 036) . The bidirectional analysis did not suggest reverse causality between cancer risk and lipid levels. Strict MR methods demonstrated the robustness of the above causal relationships. Conclusion Our findings underscore the significant causal relationships between specific lipidomic traits and the risk of developing various digestive system cancers, highlighting the potential of lipid profiles in informing cancer *Correspondence: Jun Wang [wangjunoscar@zju.edu.cn](wangjunoscar@zju.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Jin et al. Lipids in Health and Disease (2024) 23:202 Page 2 of 11 prevention and treatment strategies. These results reinforce the value of MR in unrave

FAQs

What problem does the study address about lipidomics and digestive system cancers?

It addresses uncertainty about whether specific lipid profiles causally influence the risk of digestive system cancers, rather than showing only correlation.

Which cancers and lipidomic traits are examined using Mendelian randomization?

The analysis covers stomach, liver, esophageal, pancreatic, and colorectal cancers and evaluates causal effects of multiple lipidomic traits derived from public genetic databases.

What key causal associations were reported in the results?

Higher sphingomyelin (d40:1) related to lower gastric cancer risk, while phosphatidylcholine (16:1_20:4) related to higher esophageal cancer risk; phosphatidylcholine (18:2_0:0) showed protection against colorectal cancer.

Sep 21, 2026

Uploaded by Violet