title: Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas.
abstract: The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054-0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.
authors.affiliation: Department of Neuroscience, Neurology, University Hospital, 75185 Uppsala, Sweden. shala.berntsson@hotmail.com
authors.forename: Shala Ghaderi
authors.initials: SG
authors.lastname: Berntsson
authors.forename: Carl
authors.initials: C
authors.lastname: Wibom
authors.forename: Sara
authors.initials: S
authors.lastname: Sjöström
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Thomas
authors.initials: T
authors.lastname: Brännström
authors.forename: Helle
authors.initials: H
authors.lastname: Broholm
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansson
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Fleming
authors.forename: Patricia A
authors.initials: PA
authors.lastname: McKinney
authors.forename: Lara
authors.initials: L
authors.lastname: Bethke
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
authors.forename: Anja
authors.initials: A
authors.lastname: Smits
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Melin
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005838:Genotype; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models
chemical_list: D000970:Antineoplastic Agents; D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes