Higher Plasma Levels Of Lyso-PC 18:0 Are Related To A Lower Risk Of Common Cancers In A Prospective Metabolomics Study

Tilman KÜHN, German Cancer Research Center (DKFZ), Germany
FLOEGEL A. 2 , SOOKTHAI D. 1 , JOHNSON T. 1 , ROLLE-KAMPCZYK U. 3 , OTTO W. 4 , VON BERGEN M. 3,4,5 , BOEING H. 2 , KAAKS R. 1

1 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
2 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
3 Department of Metabolomics, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany
4 Department of Proteomics, Helmholtz Centre for Environmental Research (UFZ),Leipzig, Germany
5 University of Aalborg, Aalborg East, Denmark

Purpose: First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand etiological links between metabolism and cancer. However, there is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk.
  
Methods: Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids, biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal cancer were evaluated by Cox regression analyses using data of a case-cohort sample from the EPIC-Heidelberg study including 835 incident cancer cases.

Results: The median follow-up duration was 8.2 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lyso-phosphatidylcholines (LysoPCs), and especially LysoPC a C18:0 were consistently related to lower risks of breast, prostate and colorectal cancer, independent of background factors. In contrast, higher levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity in the observed associations by lag time between blood draw and cancer diagnosis.

Conclusion: Shifts in blood lipid composition precede the manifestation of common malignancies several years prior to diagnosis. Considering the consistency of the present results across three cancer types the observed alterations point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis.

Funding source: The present metabolomics project was supported by the Helmholtz Association (Portfolio Theme “Metabolic Dysfunction”). The EPIC-Heidelberg study was further supported by the German Federal Ministry of Education and Research (BMBF) (Grant number 01ER0809).