Carcinogenesis Advance Access originally published online on March 26, 2007
Carcinogenesis 2007 28(9):1906-1913; doi:10.1093/carcin/bgm073
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma
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
1 Neurosurgery Department of Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China
2 Department of Social Medicine, University of Bristol, Bristol, UK
3 Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
4 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
* To whom correspondence should be addressed. Email: drlu{at}fudan.edu.cn;
Correspondence may also be addressed to F.Huang; Email: huangfengping_neuro{at}hotmail.com
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.
Abbreviations: CI, confidence interval; CVC, cross-validation consistency; DNA–PK, DNA-dependent protein kinase; DSB, double-strand DNA break; IR, ionizing radiation; LD, linkage disequilibrium; MDR, multifactor dimensionality reduction; NHEJ, non-homologous end joining; OR, odds ratio; tSNP, tagging single-nucleotide polymorphism
These authors contribute equally to this work. Received January 31, 2007; revised March 15, 2007; accepted March 21, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. McKean-Cowdin, J. Barnholtz-Sloan, P. D. Inskip, A. M. Ruder, M. Butler, P. Rajaraman, P. Razavi, J. Patoka, J. K. Wiencke, M. L. Bondy, et al. Associations between Polymorphisms in DNA Repair Genes and Glioblastoma Cancer Epidemiol. Biomarkers Prev., April 1, 2009; 18(4): 1118 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, M. E. Scheurer, R. El-Zein, Y. Cao, K.-A. Do, M. Gilbert, K. D. Aldape, Q. Wei, C. Etzel, and M. L. Bondy Association and Interactions between DNA Repair Gene Polymorphisms and Adult Glioma Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 204 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Hu, H. Liu, H. Wang, R. Miao, W. Sun, G. Jin, Y. Wang, H. Ma, L. Jin, Q. Wei, et al. Tagging Single Nucleotide Polymorphisms in Phosphoinositide-3-Kinase-Related Protein Kinase Genes Involved in DNA Damage "Checkpoints" and Lung Cancer Susceptibility Clin. Cancer Res., May 1, 2008; 14(9): 2887 - 2891. [Abstract] [Full Text] [PDF]
|
|