Correlation between X-ray cross-complementing group 1 polymorphisms and the onset risk of gliomaA meta-analysis******

    loading  Checking for direct PDF access through Ovid

Abstract

OBJECTIVE:

To evaluate the association of X-ray cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp and Arg280His polymorphisms with the risk of glioma.

DATA SOURCES:

A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang database was performed. The key words used were “glioma”, “polymorphism”, and “XRCC1 or X-ray repair cross-complementing group 1”. References cited in the retrieved articles were screened manually to identify additional eligible studies.

STUDY SELECTION:

Studies were identified according to the following inclusion criteria: case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger's test using Stata 12.0 software.

MAIN OUTCOME MEASURES:

Association of XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to different ethnicities of the subjects.

RESULTS:

Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399Gln polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model (Gln/Gln + Gln/Arg versus Arg/Arg: OR = 1.26, 95% CI = 1.03-1.54, P = 0.02). In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive (OR = 1.46, 95%CI = 1.04-2.45, P = 0.03) and dominant models (OR = 1.40, 95%CI = 1.10-1.78, P = 0.007), and homozygote contrast (OR = 1.69, 95%CI = 1.17-2.45, P = 0.005), but not in Caucasian subjects. For association of the Arg194Trp (eight studies) and Arg280His (four studies) polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast.

CONCLUSION:

The XRCC1 Arg399Gln polymorphism may be a biomarker of glioma susceptibility, especially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.

Research Highlights

(1) Evidence for the role of single nucleotide polymorphisms of the X-ray cross-complementing group 1 (XRCC1) gene as genetic markers for glioma risk is conflicting. Therefore, we performed a meta-analysis to identify statistical evidence for an association between the XRCC1 Arg399Gln, Arg194Trp, Arg280His polymorphisms and glioma risk by accumulating all published data.

Research Highlights

(2) Experimental design was strict and reasonable, and every possible mode of inheritance was considered. Dominant and recessive genetic models were assumed and, at the same time, the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated.

Research Highlights

(3) Meta-analysis results verified that the XRCC1 Arg399Gln polymorphism may be a biomarker of glioma susceptibility, especially in Asian populations. The Arg194Trp and Arg280His polymorphisms were found not to be associated with overall glioma risk.

Related Topics

    loading  Loading Related Articles