Endothelial nitric oxide synthase gene polymorphisms modulate the risk of squamous cell carcinoma of head and neck in north Indian population

Abstract Background Nitric oxide (NO) is found to have both tumour promoting and inhibiting properties. Nitric oxide (NO) is synthesized by three isoforms of nitric oxide synthase (NOS) enzymes and endothelial NOS ( eNOS ) is one of them. Polymorphisms in eNOS 894G u003e T (rs1799983) and eNOS intron 4a/b geneS could modulate the risk for developing SCCHN by regulating the level of nitric oxide. Objective In this study we evaluated the association of eNOS 894G u003e T (rs1799983) and intron 4a/b polymorphisms with the plasma nitrite level and the risk of Squamous cell carcinoma of the head and neck (SCCHN). Materials and methods A total of 352 subjects were genotyped for the above said polymorphisms. Genotypes were correlated with plasma nitrite level of study subjects. Results Compared to GG homozygote of 894G u003e T polymorphism a significantly increased risk of SCCHN was observed with TT homozygote (p = 0.03, OR = 2.72, 95% CI 1.14–6.50). In comparison to carrier of ‘b’ allele, ‘a’ allele carrier for intron 4a/b polymorphism were at increased risk to develop high stage diseases (p = 0.00, OR 8.67 and 95% CI 3.76–19.99). The haplotype bT constituted from 894G u003e T and intron 4a/b polymorphisms also showed association with increased susceptibility for SCCHN (p = 0.038 OR = 1.66, 95% CI 1.03–2.63). Plasma nitrite level was significantly higher in cases compared to control (p = 0.047). The level of plasma nitrite was also higher in individuals with TT genotype compared to those with GG genotype (p = 0.012 in SCCHN cases and 0.088 in control). Conclusions: Our results suggest that eNOS 894G u003e T and intron 4a/b polymorphisms influence the risk of SCCHN and, eNOS 894G u003e T polymorphism modulate the risk of disease by modulating plasma nitrite level.