Abstract
BackgroundFirst metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. However, there is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk.MethodsAssociations 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 prospective case-cohort study including 835 incident cancer cases.ResultsThe median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lysophosphatidylcholines (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.ConclusionChanges in blood lipid composition precede the diagnosis of common malignancies by several years. 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0552-3) contains supplementary material, which is available to authorized users.
Highlights
First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer
First prospective metabolomics studies have shown that elevations in circulating branched-chained amino acids 2–5 years prior to diagnosis are related to increased risk of pancreatic adenocarcinoma [2], that significant differences in serum levels of phosphatidylcholines and fatty acids between
Analyses on breast cancer risk were adjusted for menopausal status, current hormone replacement therapy (HRT) use, current oral contraceptive use, and at least one full term pregnancy
Summary
First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. There is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk. The simultaneous measurement of a large variety of small molecules in accessible tissues by metabolomics techniques may facilitate the identification of metabolic fingerprints of different cancers [1]. We report results of the largest prospective metabolomics study so far on cancers of the breast, colorectum, and prostate. Kühn et al BMC Medicine (2016) 14:13 case-cohort subset of the prospective population-based EPIC-Heidelberg study, we analyzed pre-diagnostic levels of 120 plasma metabolites by liquid chromatographytandem mass spectrometry (LC-MS/MS) and flow injection analysis-tandem mass spectrometry (FIA-MS/MS), and evaluated associations between these metabolites and cancer risk over time
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