Polymorphisms of the neuronal and inducible nitric oxide synthase genes and the risk of cutaneous melanoma: A case-control study

BACKGROUND. Nitric oxide (NO) is a multifunctional molecule that is produced by both neuronal NO synthase (nNOS) and inducible NO synthase (iNOS), and the expression of nNOS and iNOS is up-regulated in various cancer cells, including cutaneous melanoma (CM). The authors hypothesized that selected functional single-nucleotide polymorphisms (SNPs) in the nNOS and iNOS genes are associated with the risk of CM. METHODS. In a hospital-based case-control study of 602 non-Hispanic white patients with CM and 603 matched, cancer-free controls, the authors genotyped the nNOS -84 guanine-to-adenine (G→A), nNOS 276 cytosine-to-thymine (C→T), iNOS Ex16+14C→T, and iNOS 974G→T SNPs and assessed their associations with the risk of CM in multivariate logistic regression models. RESULTS. A significantly increased risk of CM was associated with the nNOS -84G→A (adjusted odds ratio [OR], 1.49; 95% confidence interval [95% CI], 1.05-2.13) and -84AG+AA (OR, 1.48; 95% CI, 1.06-2.06) genotypes compared with the nNOS -84GG genotype, but not with other nNOS or iNOS SNPs. In a combined analysis, an increased risk of CM was associated with the nNOS -84AA+AG/ 276CT+TT genotype (OR, 1.70; 95% CI, 1.05-2.76) and the nNOS -84AA+AG/ 276CC genotype (OR, 1.70; 95% CI, 1.08-2.68) compared with the nNOS -84GG/ 276CT+TT genotypes. No altered risk of CM was associated with iNOS genotypes. In addition, there was statistical evidence of interaction of nNOS SNPs with having moles (P = .002) and sunburns (P = .017). CONCLUSIONS. Genetic variants of nNOS, but not iNOS, may be biomarkers for susceptibility to CM, and the risk of CM associated with sunburns and moles may be modulated by nNOS variant genotypes.