Associations between ERCC2 polymorphisms and gliomas

Xeroderma pigmentosum complementation group D/excision repair cross-complem enting in rodents 2 (ERCC2) encodes a protein that is part of the nucleotid e excision repair pathway and the transcription factor IIH transcription co mplex. Mutations in this gene have been shown to cause three distinct clini cal diseases including xeroderma pigmentosum, Cockayne syndrome, and tricho thiodystrophy. Several ERCC2 polymorphisms, the effects of which on gene fu nction are not known, have been described. To investigate whether constitut ive sequence variations might be associated with adult onset gliomas, blood specimens from a case-control study (187 cases and 169 controls) were geno typed for seven previously described polymorphisms (R156R, I199M, H201Y, D3 12N, A575A, D711D, and K751Q). A novel R616C polymorphism was also identifi ed. Cases were significantly more likely than controls to be homozygous for the silent AA variant at codon 156 (odds ratio, 2.3; 95% confidence interv al, 1.3-4.2). Although this was observed for patients in each of three hist ological subgroups of cases, (glioblastoma multiforme, astrocytoma, and oli goastrocytoma) compared with controls, the association was strongest for pa tients 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 fo r any subgroup after adjustment for age and gender. Individuals with varian t 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. Althoug h the pattern of association observed here is consistent with a role of ERC C2 variants in the prevention or causation of glioma, these results are als o consistent with the possibility that another gene linked to ERCC2 may be involved. This seems especially so because the strongest association was ob served,vith a silent nucleotide variation.