Association between the XRCC6 Promoter rs2267437 polymorphism and cancer risk: evidence based on the current literature

Abstract

Background: Increasing evidence suggests that the DNA repair gene XRCC6 (Ku70) may be critically involved in the aetiology of the human carcinogenesis. Many studies have investigated the association between the rs2267437 polymorphism and cancer susceptibility. However, the results of these studies have been controversial. This meta-analysis was conducted to quantitatively summarize the evidence for a relationship between the rs2267437 polymorphism and cancer risk.

Methods: Electronic databases, including PUBMED and EMBASE, were searched for publications that met the inclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between the XRCC6 promoter rs2267437 polymorphism and cancer risk in a fixed-effects model (the Mantel-Haenszel method) or a random-effects model (the DerSimonian and Laird method), as appropriate.

Results: A total of 13 case-control studies, involving 3675 cases and 4247 controls, investigating the XRCC6 rs2267437 polymorphism and cancer susceptibility were identified for the meta-analysis. The pooled analysis showed that there is a significant relationship between the XRCC6 rs2267437 polymorphism and cancer susceptibility (GG vs. CC: OR=1.28, 95% CI=1.03-1.60). Subgroup analyses based on the cancer type, ethnicity, and source of the controls were also performed, and these results indicated that the XRCC6 promoter rs2267437 polymorphism was associated with cancer risk in breast cancer studies (GG vs. CC: OR=1.79, 95% CI=1.25-2.56; GG vs. CG+CC: OR=1.40, 95% CI=1.01-1.95), in Asian populations (GG vs. CC: OR=1.33, 95% CI=1.01-1.74) and in population-based studies (GG vs. CC: OR=1.57, 95% CI=1.12-2.22; CG vs. CC: OR=1.35, 95% CI=1.11-1.64; GG+CG vs. CC: OR=1.37, 95% CI=1.14-1.65).

Conclusion: This meta-analysis suggests that the XRCC6 rs2267437 polymorphism may affect breast cancer susceptibility and increase the risk of cancer in Asian populations and in the general population. It is critical that further large-scale and well-designed studies be conducted to confirm the association between the rs2267437 genotype and cancer risk.

FIG. 1.

Studies identified with criteria for inclusion and exclusion.

FIG. 2.

Forest plots of 13 individual studies of the XRCC6 rs2267437 polymorphism and cancer risk in a codominant model (GG vs. CC). The squares and horizontal lines correspond to the study-specific OR and 95% confidence interval (CI). The area of the squares indicates the study-specific weight. The diamond represents the pooled OR and 95% CI.

FIG. 3.

Forest plots of studies stratified by study type (GG vs. CC). The squares and horizontal lines correspond to the study-specific OR and 95% confidence interval (CI). The diamond reflects the pooled OR and 95% CI.

FIG. 4.

Influence analysis of GG versus CC in this meta-analysis.

FIG. 5.

The Begg's funnel plot to detect publication bias.