XRCC1 and XRCC3 variants and risk of glioma and meningioma.
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.
Kiuru
Anne
A
Department of Research and Environmental Surveillance, STUK-Radiation and Nuclear Safety Authority, Box 14, 00881 Helsinki, Finland. anne.kiuru@stuk.fi
Lindholm
Carita
C
Heinävaara
Sirpa
S
Ilus
Taina
T
Jokinen
Päivi
P
Haapasalo
Hannu
H
Salminen
Tiina
T
Christensen
Helle Collatz
HC
Feychting
Maria
M
Johansen
Christoffer
C
Lönn
Stefan
S
Malmer
Beatrice
B
Schoemaker
Minouk J
MJ
Swerdlow
Anthony J
AJ
Auvinen
Anssi
A
D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005060:Europe / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008579:Meningioma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012306:Risk; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human