Nitric Oxide Synthase 3 Gene Variants and Colorectal Cancer: a Meta-Analysis

Background: Colorectal cancer (CRC) is the worldwide disease which causes enormous losses every year. Recent studies suggested that environmental and gene factors might be the etiologies in increasing the risk of morbidity. Nitric oxide synthase 3 (NOS3) gene polymorphisms are said to be associated with CRC risk but the conclusion is still controversial. Materials and Methods: Pubmed and HuGENet databases up to December 2013 were used in this meta-analysis. Three different certain genotypic models were applied, namely dominant (AA+AC versus CC), recessive (AA versus AC+CC), per-allele analysis (A vs C). In addition, information on tumor sites and pathologic stages was collected. The strength of associations was assessed through combining odds ratio (OR) and 95% confidence interval (CI). Results: Finally, five and three studies about the rs1799983 and rs2070744 were covered in the analysis with 2,745 cases and 2,478 controls. Three models were applied, but no significant association was found for NOS3 G894T/rs1799983 (dominant: OR=0.999, 95%CI=0.797-1.253, $I^2$=63.8%; recessive: OR=0.924, 95%CI=0.589-1.450, $I^2$=59.3%; allele analysis: OR=0.979, 95%CI=0.788-1.216, $I^2$=74.9%) and T-786C/rs2070744 (dominant: OR=1.138, 95%CI=0.846-1.530, $I^2$=67.9%; recessive: OR=0.956, 95%CI=0.708-1.291, $I^2$=0.0%; allele analysis: OR=1.110, 95%CI=0.865-1.425, $I^2$=69.4%). The same results were also obtained for tumor sites and pathologic stage subgroups. After further analyzing the NOS3 gene, rs1799983 as the tag- and functional SNP was presented. Conclusions: On the basis of this meta-analysis and the characteristics of the NOS3 gene, we suggested rs1799983 might be a key locus associated with CRC risk. Further prospective studies were needed to make more comprehensive explanation of the associations.