Oncotarget

Research Papers:

A prospective study of serum metabolites and glioma risk

Jiaqi Huang, Stephanie J. Weinstein, Cari M. Kitahara, Edward D. Karoly, Joshua N. Sampson and Demetrius Albanes _

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Oncotarget. 2017; 8:70366-70377. https://doi.org/10.18632/oncotarget.19705

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Abstract

Jiaqi Huang1, Stephanie J. Weinstein1, Cari M. Kitahara2, Edward D. Karoly3, Joshua N. Sampson4 and Demetrius Albanes1

1Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD, USA

2Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD, USA

3Director of Project Management, Metabolon, Inc., Morrisville, NC, USA

4Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD, USA

Correspondence to:

Demetrius Albanes, email: [email protected]

Keywords: malignant glioma, metabolomics, prospective, arginine/proline metabolism, antioxidant

Received: April 23, 2017     Accepted: June 29, 2017     Published: July 31, 2017

ABSTRACT

Malignant glioma is one of the most lethal adult cancers, yet its etiology remains largely unknown. We conducted a prospective serum metabolomic analysis of glioma based on 64 cases and 64 matched controls selected from Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Median time from collection of baseline fasting serum to diagnosis was nine years (inter-decile range 3-20 years). LC/MS-MS identified 730 known metabolites, and conditional logistic regression models estimated odds ratios for one-standard deviation differences in log-metabolite signals. Forty-three metabolites were associated with glioma at P<0.05. 2-Oxoarginine, cysteine, alpha-ketoglutarate, chenodeoxycholate and argininate yielded the strongest metabolite signals and were inversely related to overall glioma risk (0.0065≤P<0.0083). Also, seven xanthine metabolites related to caffeine metabolism were higher in cases than in controls (0.017≤P<0.042). Findings were mostly similar in high-grade glioma cases, although prominent inversely associated metabolites included the secondary bile acids glycocholenate sulfate and 3β-hydroxy-5-cholenoic acid, xenobiotic methyl 4-hydroxybenzoate sulfate, sex steroid 5alpha-pregnan-3beta, 20beta-diol-monosulfate, and cofactor/vitamin oxalate (0.0091≤P<0.021). A serum metabolomic profile of glioma identified years in advance of clinical diagnoses is characterized by altered signals in arginine/proline, antioxidant, and coffee-related metabolites. The observed pattern provides new potential leads regarding the molecular basis relevant to etiologic or sub-clinical biomarkers for glioma.


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