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ORIGINAL RESEARCH article

Front. Nutr.
Sec. Clinical Nutrition
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1501263

Lipoprotein Subclasses and Gastrointestinal Cancers: Novel Perspectives and Potential Associations

Provisionally accepted
Chuang Yang Chuang Yang 1Dong Liu Dong Liu 2Yong Wang Yong Wang 3Feng Cao Feng Cao 2*
  • 1 Leipzig University, Leipzig, Lower Saxony, Germany
  • 2 University Hospital RWTH Aachen, Aachen, Germany
  • 3 Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Background: This study aimed to investigate the associations between serum lipoprotein subclasses and the long-term risk of gastrointestinal (GI) cancers to enhance our understanding of the etiology of GI cancers.This prospective cohort study included 249,450 participants from the UK Biobank. Cox proportional hazard models were used to assess the association between 17 serum lipoprotein subclasses with the risk of GI cancers. Restricted cubic spline (RCS) analysis was employed to assess the corresponding dose-response relationships. Additionally, Mendelian randomization (MR) analysis was used to evaluate the causal relationships between the lipoproteins and the risk of GI cancers.Results: A total of 4,787 cases of GI cancers were recorded over a median follow-up period of 12.92 years. Our results revealed that the majority of the high-density lipoprotein (HDL) subclasses, such as very large-, large-, and medium-HDL-particles, were positively associated, while several low-density lipoprotein (LDL) subclasses were negatively associated with the risk of overall GI cancer. Additionally, RCS analysis revealed a linear dose-response relationship between elevated levels of most lipoprotein particles and the risk of overall GI cancer development. Additionally, subgroup analysis indicated a significant sex-dependent interaction between lipoprotein particles and the risk of GI cancers. However, MR analysis revealed a different causal relationships between lipoprotein and GI cancers at the genetic level.In this large-scale metabolomics study, we identified several associations between lipoprotein subclasses and the long-term risk of GI cancers.However, further research is needed to fully elucidate their roles in the mechanisms of cancer development.

    Keywords: Lipoprotein subclasses, gastrointestinal (GI) cancers, UK Biobank (UKB), Mendelian Randomization (MR), Metabolomics

    Received: 24 Sep 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Yang, Liu, Wang and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Feng Cao, University Hospital RWTH Aachen, Aachen, Germany

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