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)

Rhea Harewood*, Joseph A Rothwell, Jelena Bešević, Vivian Viallon, David Achaintre, Audrey Gicquiau, Sabina Rinaldi, Roland Wedekind, Cornelia Prehn, Jerzy Adamski, Julie A Schmidt, Inarie Jacobs, Anne Tjønneland, Anja Olsen, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B Schulze, Marcela Prada, Giovanna MasalaClaudia Agnoli, Salvatore Panico, Carlotta Sacerdote, Paula Gabriela Jakszyn, Maria-Jose Sánchez, Jesús Castilla, María-Dolores Chirlaque, Amaia Aizpurua Atxega, Bethany van Guelpen, Alicia K Heath, Keren Papier, Tammy Y N Tong, Scott A Summers, Mary Playdon, Amanda J Cross, Pekka Keski-Rahkonen, Véronique Chajès, Neil Murphy, Marc J Gunter

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


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 acylakyl-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. Funding: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

Original languageEnglish
Article number105024
Number of pages15
Publication statusPublished - Mar 2024


  • Acylcarnitines
  • Colorectal cancer
  • Glycerophospholipids
  • Lipids
  • Metabolomics
  • Sphingolipids
  • Prospective Studies
  • Phosphatidylcholines/metabolism
  • Humans
  • Risk Factors
  • Male
  • Case-Control Studies
  • Colorectal Neoplasms/diagnosis
  • Female


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