TY - JOUR

T1 - Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk

T2 - a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)

AU - Harewood, Rhea

AU - Rothwell, Joseph A

AU - Bešević, Jelena

AU - Viallon, Vivian

AU - Achaintre, David

AU - Gicquiau, Audrey

AU - Rinaldi, Sabina

AU - Wedekind, Roland

AU - Prehn, Cornelia

AU - Adamski, Jerzy

AU - Schmidt, Julie A

AU - Jacobs, Inarie

AU - Tjønneland, Anne

AU - Olsen, Anja

AU - Severi, Gianluca

AU - Kaaks, Rudolf

AU - Katzke, Verena

AU - Schulze, Matthias B

AU - Prada, Marcela

AU - Masala, Giovanna

AU - Agnoli, Claudia

AU - Panico, Salvatore

AU - Sacerdote, Carlotta

AU - Jakszyn, Paula Gabriela

AU - Sánchez, Maria-Jose

AU - Castilla, Jesús

AU - Chirlaque, María-Dolores

AU - Atxega, Amaia Aizpurua

AU - van Guelpen, Bethany

AU - Heath, Alicia K

AU - Papier, Keren

AU - Tong, Tammy Y N

AU - Summers, Scott A

AU - Playdon, Mary

AU - Cross, Amanda J

AU - Keski-Rahkonen, Pekka

AU - Chajès, Véronique

AU - Murphy, Neil

AU - Gunter, Marc J

N1 - Copyright © 2024. Published by Elsevier B.V.

PY - 2024

Y1 - 2024

N2 - 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 (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).

AB - 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 (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).

KW - Humans

KW - Female

KW - Male

KW - Prospective Studies

KW - Risk Factors

KW - Case-Control Studies

KW - Colorectal Neoplasms/diagnosis

KW - Sphingolipids

KW - Phosphatidylcholines/metabolism

U2 - 10.1016/j.ebiom.2024.105024

DO - 10.1016/j.ebiom.2024.105024

M3 - Journal article

C2 - 38412638

VL - 101

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

M1 - 105024

ER -