Pre-Diagnostic Metabolite Concentrations Related to Cancer Risk

Prostate cancer is the second most commonly diagnosed cancer in men worldwide, but circulating insulin-like growth factor I is the only established risk factor that is potentially modifiable.

The prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumor characteristics, and risk of death from prostate cancer has been investigated. Examination of the metabolome may help identify novel risk factors for prostate cancer.

A large team of scientists collaborating with those at the Nuffield Department of Population Health (Oxford, UK) recruited 153,400 men from 19 centers in eight European countries. At recruitment, detailed information was collected on dietary intake, lifestyle, anthropometry and previous disease, and 139,600 men also gave a blood sample. Histological grade was known for 83.8% of cases and information on tumor stage was available for 61.7% of cases.

All plasma samples (citrate anticoagulant) were assayed using the AbsoluteIDQ p180 Kit. Pre-diagnostic plasma concentrations of 122 metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids, were measured using targeted mass spectrometry and compared between 1,077 prostate cancer cases and 1,077 matched controls. A triple quadrupole mass spectrometer was used to quantify the metabolites. The concentration of total prostate-specific antigen (PSA) at baseline was measured and was available for 71.1% of men in the current study, including 764 controls, for whom 489 had a concentration below 1 ng/mL, and 768 cases.

The scientists found seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer, but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration. Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4.

The authors concluded that several metabolites. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1 might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to etiology. Several glycerophospholipids were inversely related to advanced stage disease. The study was published on July 5, 2017, in the journal BMC Medicine.

Related Links:
Nuffield Department of Population Health