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 - Publisher Copyright:
© 2024
PY - 2024/3
Y1 - 2024/3
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 - Acylcarnitines
KW - Colorectal cancer
KW - Glycerophospholipids
KW - Lipids
KW - Metabolomics
KW - Sphingolipids
UR - http://www.scopus.com/inward/record.url?scp=85187658965&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2024.105024
DO - 10.1016/j.ebiom.2024.105024
M3 - Article
C2 - 38412638
AN - SCOPUS:85187658965
SN - 2352-3964
VL - 101
JO - eBioMedicine
JF - eBioMedicine
M1 - 105024
ER -
