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).
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Harewood Rhea, Rothwell Joseph A, Bešević Jelena, Viallon Vivian, Achaintre David, Gicquiau Audrey, Rinaldi Sabina, Wedekind Roland, Prehn Cornelia, Adamski Jerzy, Schmidt Julie A, Jacobs Inarie, Tjønneland Anne, Olsen Anja, Severi Gianluca, Kaaks Rudolf, Katzke Verena, Schulze Matthias B, Prada Marcela, Masala Giovanna, Agnoli Claudia, Panico Salvatore, Sacerdote Carlotta, Jakszyn Paula Gabriela, Sánchez Maria-Jose, Castilla Jesús, Chirlaque María-Dolores, Atxega Amaia Aizpurua, van Guelpen Bethany, Heath Alicia K, Papier Keren, Tong Tammy Y N, Summers Scott A, Playdon Mary, Cross Amanda J, Keski-Rahkonen Pekka, Chajès Véronique, Murphy Neil, Gunter Marc J
Аннотация
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 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper 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).