Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma.
Ionizing radiation is known to cause DNA damage, including single-strand and double-strand DNA breaks (DSBs), and the unrepair of DNA damage, particularly DSBs, may cause chromosome aberrations. Although the etiology of gliomas remains unclear, exposure to ionizing radiation has been identified as the only established risk factor. We hypothesized that polymorphisms of candidate genes involved in the DSBs repair pathway may contribute to susceptibility to glioma. We used a haplotype-based approach to investigate the role of 22 tagging single-nucleotide polymorphisms (tSNPs) of XRCC5, XRCC6 and XRCC7 in 771 glioma patients and 752 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, haplotypes were inferred by the HAPLO.STAT program and gene-gene interactions were evaluated by the multifactor dimensionality reduction method. We found that, in the single-locus analysis, glioma risk was statistically significantly associated with three XRCC5 tSNPs (SNP1 rs828704, SNP6 rs3770502 and SNP7 rs9288516, P = 0.005, 0.042 and 0.003, respectively), one XRCC6 tSNP (SNP4 rs6519265, P = 0.044) but none of XPCC7 tSNPs. Haplotype-based association analysis revealed that gliomas risk was statistically significantly associated with one protective XRCC5 haplotype "CAGTT," accounting for a 40% reduction (OR = 0.60, 95% CI = 0.43-0.85) in glioma risk, and some positive gene-gene interactions were also evident. In conclusion, genetic variants of the genes involved in the DSB repair pathway may play a role in the etiology of glioma.
Liu
Yanhong
Y
State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes for Biomedical Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
Zhang
Haishi
H
Zhou
Keke
K
Chen
Lina
L
Xu
Zhonghui
Z
Zhong
Yu
Y
Liu
Hongliang
H
Li
Rui
R
Shugart
Yin Yao
YY
Wei
Qingyi
Q
Jin
Li
L
Huang
Fengping
F
Lu
Daru
D
Zhou
Liangfu
L
D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002874:Chromosome Mapping; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005838:Genotype; D005910:Glioma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D019869:Phosphatidylinositol 3-Kinases; D004265:DNA Helicases