title: Associations between ERCC2 polymorphisms and gliomas.
abstract: Xeroderma pigmentosum complementation group D/excision repair cross-complementing in rodents 2 (ERCC2) encodes a protein that is part of the nucleotide excision repair pathway and the transcription factor IIH transcription complex. Mutations in this gene have been shown to cause three distinct clinical diseases including xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Several ERCC2 polymorphisms, the effects of which on gene function are not known, have been described. To investigate whether constitutive sequence variations might be associated with adult onset gliomas, blood specimens from a case-control study (187 cases and 169 controls) were genotyped for seven previously described polymorphisms (R156R, I199M, H201Y, D312N, A575A, D711D, and K751Q). A novel R616C polymorphism was also identified. Cases were significantly more likely than controls to be homozygous for the silent AA variant at codon 156 (odds ratio, 2.3; 95% confidence interval, 1.3-4.2). Although this was observed for patients in each of three histological subgroups of cases, (glioblastoma multiforme, astrocytoma, and oligoastrocytoma) compared with controls, the association was strongest for patients with oligoastrocytoma (odds ratio, 3.2; 95% confidence interval, 1.1-9.5). In contrast, cases were somewhat less likely than controls to carry variants at D312N, D711D, and K751Q, but not significantly so overall or for any subgroup after adjustment for age and gender. Individuals with variant nucleotides at D312N, D711D, and K751Q were significantly more likely to carry a variant at another of those three codons and less likely to carry a variant nucleotide at R156R, regardless of case or control status. Although the pattern of association observed here is consistent with a role of ERCC2 variants in the prevention or causation of glioma, these results are also consistent with the possibility that another gene linked to ERCC2 may be involved. This seems especially so because the strongest association was observed with a silent nucleotide variation.
authors.affiliation: Division of Genetic Disorders, New York State Department of Health, Wadsworth Center, Albany 12201-0509, USA.
authors.forename: M
authors.initials: M
authors.lastname: Caggana
authors.forename: J
authors.initials: J
authors.lastname: Kilgallen
authors.forename: J M
authors.initials: JM
authors.lastname: Conroy
authors.forename: J K
authors.initials: JK
authors.lastname: Wiencke
authors.forename: K T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: R
authors.initials: R
authors.lastname: Miike
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: M R
authors.initials: MR
authors.lastname: Wrensch
mesh_terms: D000328:Adult; D017668:Age of Onset; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human