Li Chunying, Hu Zhibin, Liu Zhensheng, Wang Li-E, Gershenwald Jeffrey E, Lee Jeffrey E, Prieto Victor G, Duvic Madeleine, Grimm Elizabeth A, Wei Qingyi
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2007 Apr 15;109(8):1570-8. doi: 10.1002/cncr.22582.
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.
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.
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).
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.
一氧化氮（NO）是一种多功能分子，由神经元型一氧化氮合酶（nNOS）和诱导型一氧化氮合酶（iNOS）产生，nNOS和iNOS的表达在包括皮肤黑色素瘤（CM）在内的各种癌细胞中上调。作者推测，nNOS和iNOS基因中特定的功能性单核苷酸多态性（SNP）与CM风险相关。
在一项基于医院的病例对照研究中，纳入602例非西班牙裔白人CM患者和603例匹配的无癌对照，作者对nNOS -84鸟嘌呤到腺嘌呤（G→A）、nNOS 276胞嘧啶到胸腺嘧啶（C→T）、iNOS Ex16+14C→T和iNOS 974G→T SNP进行基因分型，并在多因素逻辑回归模型中评估它们与CM风险的关联。
与nNOS -84GG基因型相比，nNOS -84G→A（调整优势比[OR]，1.49；95%置信区间[95%CI]，1.05 - 2.13）和-84AG+AA（OR，1.48；95%CI，1.06 - 2.06）基因型与CM风险显著增加相关，但与其他nNOS或iNOS SNP无关。在综合分析中，与nNOS -84GG/276CT+TT基因型相比，nNOS -84AA+AG/276CT+TT基因型（OR，1.70；95%CI，1.05 - 2.76）和nNOS -84AA+AG/276CC基因型（OR，1.70；95%CI，1.08 - 2.68）与CM风险增加相关。iNOS基因型与CM风险改变无关。此外，有统计学证据表明nNOS SNP与有痣（P = 0.002）和晒伤（P = 0.017）之间存在相互作用。
nNOS的基因变异而非iNOS的基因变异可能是CM易感性的生物标志物，与晒伤和痣相关的CM风险可能受nNOS变异基因型的调节。
