XRCC1 and XRCC3 variants and risk of glioma and meningioma

Anne Kiuru, Carita Lindholm, Sirpa Heinävaara, Taina Ilus, Päivi Jokinen, Hannu Haapasalo, Tiina Salminen, Helle Collatz Christensen, Maria Feychting, Christoffer Johansen, Stefan Lönn, Beatrice Malmer, Minouk J Schoemaker, Anthony J Swerdlow, Anssi Auvinen

Abstract

Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case-control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97-1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34; 95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26-8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.

Original languageEnglish
JournalJournal of Neuro-Oncology
Volume88
Issue number2
Pages (from-to)135-42
Number of pages8
ISSN0167-594X
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

Keywords

  • Brain Neoplasms/epidemiology
  • Case-Control Studies
  • DNA-Binding Proteins/genetics
  • Europe/epidemiology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Glioma/epidemiology
  • Humans
  • Male
  • Meningeal Neoplasms/epidemiology
  • Meningioma/epidemiology
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide/genetics
  • Prospective Studies
  • Risk
  • X-ray Repair Cross Complementing Protein 1

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