title: Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study.
abstract: Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associated with EGFR and ErbB2 serum levels. We assessed the associations between genetic glioma risk variants and serum concentrations of EGFR and ErbB2, as measured in pre-diagnostic cohort serum samples of 593 glioma patients and 590 matched cancer-free controls. High serum EGFR and ErbB2 levels were associated with risk of developing glioblastoma (P = 0.008; OR = 1.58, 95 % CI = 1.13-2.22 and P = 0.017, OR = 1.63, 95 % CI = 1.09-2.44, respectively). High serum ErbB2 concentration was also associated with glioma risk overall (P = 0.049; OR = 1.39, 95 % CI = 1.00-1.93). Glioma risk variants were not associated with high serum protein abundance. In contrast, the EGFR risk variant rs4947986 (T) was correlated with decreased EGFR serum levels (study cohort P = 0.024 and controls P = 0.009). To our knowledge, this is the first study showing an association of EGFR and ErbB2 serum levels with glioma more than a decade before diagnosis, indicating that EGFR and ErbB2 serum proteins are important in early gliomagenesis. However, we did not find evidence that glioma risk variants were associated with high pre-diagnostic serum concentrations of EGFR and ErbB2.
authors.affiliation: Department of Radiation Sciences, Umeå University, 901 87, Umeå, Sweden. florentin.spaeth@umu.se.|Department of Oncology, Umeå University, 901 87, Umeå, Sweden. florentin.spaeth@umu.se.
authors.forename: Florentin
authors.initials: F
authors.lastname: Späth
authors.affiliation: Department of Radiation Sciences, Umeå University, 901 87, Umeå, Sweden.|Department of Oncology, Umeå University, 901 87, Umeå, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.affiliation: Department of Radiation Sciences, Umeå University, 901 87, Umeå, Sweden.|Department of Oncology, Umeå University, 901 87, Umeå, Sweden.|Computational Life Science Cluster (CLiC), Umeå University, 901 87, Umeå, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Dahlin
authors.affiliation: Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
authors.forename: Hilde
authors.initials: H
authors.lastname: Langseth
authors.affiliation: Department of Informatics, University of Oslo, Oslo, Norway.|Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
authors.affiliation: Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
authors.forename: Tom Børge
authors.initials: TB
authors.lastname: Johannesen
authors.affiliation: Department of Medical Biosciences, Clinical Chemistry, Umeå University, 901 85, Umeå, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Grankvist
authors.affiliation: Department of Chemistry, Umeå University, 901 87, Umeå, Sweden.
authors.forename: Benny
authors.initials: B
authors.lastname: Björkblom
authors.affiliation: Department of Radiation Sciences, Umeå University, 901 87, Umeå, Sweden.|Department of Oncology, Umeå University, 901 87, Umeå, Sweden.|Computational Life Science Cluster (CLiC), Umeå University, 901 87, Umeå, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Wibom
authors.affiliation: Department of Radiation Sciences, Umeå University, 901 87, Umeå, Sweden.|Department of Oncology, Umeå University, 901 87, Umeå, Sweden.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Melin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001932:Brain Neoplasms / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005910:Glioma / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: Glioma; Pre‐diagnostic; SNP; Serum EGFR; Serum ErbB2