Genetic variants within endothelial nitric oxide synthase gene and prostate cancer: a meta-analysis

Several variants within gene-encoding endothelial isoform of nitric oxide synthase have been reported to confer prostate cancer (PCa) susceptibility and/or progression. Nevertheless, studies referring to this issue have yielded inconsistent results. In order to elucidate the involvement of these variants in prostate carcinogenesis, we have conducted a meta-analysis of previously published case-control and relevant case-only studies. Eleven studies comprising in total 3,806 cases and 4,466 controls were included in the meta-analysis which yielded evidence of association of rs2070744 (ORCC = 1.43, 95% CI 1.04-1.97; p = 0.03) and intron 4a/b variant (ORab+aa = 1.47, 95% CI 1.00-2.14; p = 0.05) with PCa risk under recessive and dominant model, respectively. Furthermore, PCa patients carrying 4a/b a allele were found to have an increased risk of cancer progression to a less differentiated form, characterized by a high Gleason score (OR = 2.29, 95% CI 1.51-3.49; p < 0.01) and to higher TNM stage (OR = 2.55, 95% CI 1.71-3.81; p < 0.01). These results support the involvement of NOS3 variants in molecular pathogenesis of PCa.