Stolzenberg-Solomon R, et al. - Researchers sought to determine the association of prediagnostic metabolites with incident pancreatic ductal adenocarcinoma (PDAC). In a nested case-control study of male smokers (372 matched case-control sets) and an independent nested case-control study that involved women and non-smokers (107 matched sets), they conducted an untargeted analysis of 554 known metabolites measured in prediagnostic serum (up to 24 years) to define their relationship with incident PDAC. The outcomes revealed a significant association of 31 metabolites with PDAC at a false discovery rate < 0.05 with 12 metabolites below the Bonferroni-corrected threshold (p < 9.04×10^–5). Following Bonferroni correction, PDAC was identified to have a positive correlation with the dipeptides glycylvaline, aspartylphenylalanine, pyroglutamylglycine, phenylalanylphenylalanine, phenylalanylleucine and tryptophylglutamate and amino acids aspartate and glutamate while there was an inverse association of the dipeptides tyrosylglutamine and α-glutamyltyrosine, fibrinogen cleavage peptide DSGEGDFXAEGGGVR and glutathione-related amino acid cysteine-glutathione disulfide with PDAC. They identified significant time-varying associations of five top metabolites, with the strongest associations observed 10–15 years after participants’ blood collection and attenuation occurred thereafter. Results thereby imply that prediagnostic metabolites linked to subclinical disease, γ-glutamyl cycle metabolism, and adiposity/insulin resistance are correlated with PDAC.