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)

Abstract

BackgroundAltered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. MethodsIn 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 1,591 incident colorectal cancer cases (55% women) and 1,591 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. FindingsOf 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 cases diagnosed <5 years 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. InterpretationElevated 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. FundingWorld Cancer Research Fund (reference:2013/1002); European Commission (FP7: BBMRI-LPC; reference:313010).