The functional polymorphism of NBS1 p.Glu185Gln is associated with an increased risk of lung cancer in Chinese populations: case-control and a meta-analysis
Abstract
NBS1 plays pivotal roles in maintaining genomic stability and cancer development. The exon variant rs1805794G>C (p.Glu185Gln) of NBS1 has been frequently studied in several association studies. However, the results were conflicting. Also, the function of this variant has never been well studied. In the current study, we performed a two centers case-control study and function assays to investigate the effect of the variant rs1805794G>C on lung cancer risk in Chinese, and a meta-analysis to summarize the data on the association between rs1805794G>C and cancer risk. We found that compared with the rs1805794GG genotype, the C genotypes (CG/CC) conferred a significantly increased risk of lung cancer in Chinese (OR=1.40, 95% CI=1.21-1.62) and interacted with medical ionizing radiation exposure on increasing cancer risk (Pinteraction=0.015). The lymphocyte cells from the C genotype individuals developed more chromatid breaks than those from the GG genotype carriers after the X-ray radiation (P=0.036). Moreover, the rs1805794C allele encoding p.185Gln attenuated NBS1's ability to repair DNA damage as the cell lines transfected with NBS1 cDNA expression vector carrying rs1805794C allele had significantly higher DNA breaks than those tra...Continue Reading
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