Premium
Polymorphisms of the neuronal and inducible nitric oxide synthase genes and the risk of cutaneous melanoma
Author(s) -
Li Chunying,
Hu Zhibin,
Liu Zhensheng,
Wang LiE,
Gershenwald Jeffrey E.,
Lee Jeffrey E.,
Prieto Victor G.,
Duvic Madeleine,
Grimm Elizabeth A.,
Wei Qingyi
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22582
Subject(s) - genotype , single nucleotide polymorphism , nitric oxide synthase , odds ratio , medicine , confidence interval , logistic regression , endocrinology , gastroenterology , microbiology and biotechnology , nitric oxide , gene , pathology , biology , genetics
Abstract 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+14 C → T , and iNOS 974 G → 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 −84 G → A (adjusted odds ratio [OR], 1.49; 95% confidence interval [95% CI], 1.05–2.13) and −84 AG + AA (OR, 1.48; 95% CI, 1.06–2.06) genotypes compared with the nNOS −84 GG genotype, but not with other nNOS or iNOS SNPs. In a combined analysis, an increased risk of CM was associated with the nNOS −84 AA + AG /276 CT + TT genotype (OR, 1.70; 95% CI, 1.05–2.76) and the nNOS −84 AA + AG /276 CC genotype (OR, 1.70; 95% CI, 1.08–2.68) compared with the nNOS −84 GG /276 CT + 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. Cancer 2007. © 2007 American Cancer Society.