title: Metabolomic screening of pre-diagnostic serum samples identifies association between α- and γ-tocopherols and glioblastoma risk.
abstract: Glioblastoma is associated with poor prognosis with a median survival of one year. High doses of ionizing radiation is the only established exogenous risk factor. To explore new potential biological risk factors for glioblastoma, we investigated alterations in metabolite concentrations in pre-diagnosed serum samples from glioblastoma patients diagnosed up to 22 years after sample collection, and undiseased controls. The study points out a latent biomarker for future glioblastoma consisting of nine metabolites (γ-tocopherol, α-tocopherol, erythritol, erythronic acid, myo-inositol, cystine, 2-keto-L-gluconic acid, hypoxanthine and xanthine) involved in antioxidant metabolism. We detected significantly higher serum concentrations of α-tocopherol (p=0.0018) and γ-tocopherol (p=0.0009) in future glioblastoma cases. Compared to their matched controls, the cases showed a significant average fold increase of α- and γ-tocopherol levels: 1.2 for α-T (p=0.018) and 1.6 for γ-T (p=0.003). These tocopherol levels were associated with a glioblastoma odds ratio of 1.7 (α-T, 95% CI:1.0-3.0) and 2.1 (γ-T, 95% CI:1.2-3.8). Our exploratory metabolomics study detected elevated serum levels of a panel of molecules with antioxidant properties as well as oxidative stress generated compounds. Additional studies are necessary to confirm the association between the observed serum metabolite pattern and future glioblastoma development.
authors.affiliation: Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Benny
authors.initials: B
authors.lastname: Björkblom
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Wibom
authors.affiliation: Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Jonsson
authors.affiliation: Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Mörén
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.affiliation: Cancer Registry of Norway, Institute of Population-Based Cancer Research, N-0304 Oslo, Norway.
authors.forename: Tom Børge
authors.initials: TB
authors.lastname: Johannesen
authors.affiliation: Cancer Registry of Norway, Institute of Population-Based Cancer Research, N-0304 Oslo, Norway.
authors.forename: Hilde
authors.initials: H
authors.lastname: Langseth
authors.affiliation: Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Antti
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Melin
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001932:Brain Neoplasms / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005909:Glioblastoma / Q000097:blood*; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D010084:Oxidation-Reduction; D024502:alpha-Tocopherol / Q000097:blood*; D024504:gamma-Tocopherol / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol
keywords: antioxidants; brain tumor; population-based; serum metabolite; vitamin E