Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk : a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Harewood, Rhea (author), Adamski, Jerzy (author)

Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods: In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (OR per doubling 0.60, 95% CI 0.47-0.77) and acylalkyl-phosphatidylcholine (PC ae) C34:3 (OR per doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. Interpretation: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations.

• Language: English
• Keywords: acylcarnitines, colorectal cancer, glycerophospholipids, lipids, metabolomics, sphingolipids
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 15 str.
• Numbering: Vol. 101, art. 105024
• PID: 20.500.12556/RUL-182325
• UDC: 61:577
• ISSN on article: 2352-3964
• DOI: 10.1016/j.ebiom.2024.105024
• COBISS.SI-ID: 199009283
• Publication date in RUL: 07.05.2026

Record is a part of a journal

• Title: EBioMedicine
• Shortened title: EBioMedicine
• Publisher: Elsevier
• ISSN: 2352-3964
• COBISS.SI-ID: 523063577

Licences

• License: CC BY-NC-ND 3.0, Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported
• Link: http://creativecommons.org/licenses/by-nc-nd/3.0/
• Description: You are free to reproduce and redistribute the material in any medium or format. You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material. You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.

Secondary language

• Language: Slovenian
• Keywords: acilkarnitini, kolorektalni rak, glicerofosfolipidi, lipidi, metabolomika, sfingolipidi

Projects

• Funder: World Cancer Research Fund
• Project number: 2013/1002

• Funder: EC - European Commission
• Project number: 313010
• Name: BBMRI - Large Prospective Cohorts
• Acronym: BBMRI-LPC