Prediagnostic circulating levels of tricarboxylic acid (TCA) cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer, according to a study of 82 metabolites in prediagnostic plasma from 484 patients with pancreatic cancer. Researchers found:

• 2 metabolites in the TCA cycle–isocitrate and aconitate–were significantly associated with survival.

• Patients in the highest vs lowest quintile had hazard ratios for death of 1.89 for isocitrate and 2.54 for aconitate.

• Isocitrate is interconverted with citrate via the intermediate phase aconitate in a reaction catalyzed by the senzyme aconitase 1 (ACO1).

• The citrate to aconitate plus isocitrate ratio was strongly associated with survival, as was the SNP rs7874815 in the ACO1 gene.

• Patients had about a 3-fold hazard for death when possessing 1 or more minor alleles at rs7874851 and high aconitate or isocitrate.

Citation: Yuan C, Clish CB, Wu C, et al. Circulating metabolites and survival among patients with pancreatic cancer. J Natl Cancer Inst. 108(6):djv409. doi: 10.1093/jnci/djv409.