Association between the NBS1 E185Q polymorphism and cancer risk: a meta-analysis

Background: NBS1 is a key DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint that plays important roles in maintaining genomic stability. The NBS1 8360G>C (Glu185Gln) is one of the most commonly studied polymorphisms of the gene for their association with risk of cancers, but the results are conflicting. Methods: We performed a meta-analysis using 16 eligible case-control studies (including 17 data sets) with a total of 9,734 patients and 10,325 controls to summarize the data on the association between the NBS1 8360G>C (E185Q) polymorphism and cancer risk. Results: Compared with the common 8360GG genotype, the carriers of variant genotypes (i.e., 8360 GC/CC) had a 1.06-fold elevated risk of cancer (95% CI = 1.00-1.12, P = 0.05) in a dominant genetic model as estimated in a fixed effect model. However, the association was not found in an additive genetic model (CC vs GG) (odds ratio, OR = 0.98, 95% CI = 0.85-1.13, P = 0.78) nor in a recessive genetic model (CC vs GC + GG) (OR = 0.94, 95% CI = 0.82-1.07, P = 0.36). The effect of the 8360G>C (E185Q) polymorphism was further evaluated in stratification analysis. It was demonstrated that the increased risk of cancer associated with 8360G>C variant genotypes was more pronounced in the Caucasians (OR = 1.07, 95% CI = 1.01-1.14, P = 0.03). Conclusion: Our meta-analysis suggests that the NBS1 E185Q variant genotypes (8360 GC/CC) might be associated with an increased risk of cancer, especially in Caucasians.