Dataset Information

Circulating Metabolites and Survival Among Patients With Pancreatic Cancer.

ABSTRACT: BACKGROUND:Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. METHODS:We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. RESULTS:Two metabolites in the tricarboxylic acid (TCA) cycle--isocitrate and aconitate--were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, Ptrend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, Ptrend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. CONCLUSIONS:Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer.

SUBMITTER: Yuan C

PROVIDER: S-EPMC4849356 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Circulating Metabolites and Survival Among Patients With Pancreatic Cancer.

Yuan Chen C Clish Clary B CB Wu Chen C Mayers Jared R JR Kraft Peter P Townsend Mary K MK Zhang Mingfeng M Tworoger Shelley S SS Bao Ying Y Qian Zhi Rong ZR Rubinson Douglas A DA Ng Kimmie K Giovannucci Edward L EL Ogino Shuji S Stampfer Meir J MJ Gaziano John Michael JM Ma Jing J Sesso Howard D HD Anderson Garnet L GL Cochrane Barbara B BB Manson JoAnn E JE Torrence Margaret E ME Kimmelman Alec C AC Amundadottir Laufey T LT Vander Heiden Matthew G MG Fuchs Charles S CS Wolpin Brian M BM

Journal of the National Cancer Institute 20160111 6

<h4>Background</h4>Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown.<h4>Methods</h4>We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, ...[more]

PMID: 26755275

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Dataset Information

Circulating Metabolites and Survival Among Patients With Pancreatic Cancer.

Publications

Circulating Metabolites and Survival Among Patients With Pancreatic Cancer.

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