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.