Most patients with
pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive
biomarkers that signal the presence of
pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic
biomarkers associated with early stages of
pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of
pancreatic cancer between 1 month and 17 years after sampling (N = 356) and age- and sex-matched controls (N = 887) were collected from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian Biobank, Rotterdam Study). We applied
proton nuclear magnetic resonance-based metabolomics on the Nightingale platform. Logistic regression identified two interesting hits:
glutamine (P = 0.011) and
histidine (P = 0.012), with Westfall-Young family-wise error rate adjusted P values of 0.43 for both. Stratification in quintiles showed a 1.5-fold elevated risk for the lowest 20% of
glutamine and a 2.2-fold increased risk for the lowest 20% of
histidine. Stratification by time to diagnosis suggested
glutamine to be involved in an earlier process (2 to 5 years before diagnosis), and
histidine in a process closer to the actual onset (<2 years). Our data did not support the
branched-chain amino acids identified earlier in several US cohorts as potential
biomarkers for
pancreatic cancer. Thus, although we identified
glutamine and
histidine as potential
biomarkers of biological interest, our results imply that a study at this scale does not yield metabolomic
biomarkers with sufficient predictive value to be clinically useful per se as prognostic
biomarkers.