Muñoz-Guerra Mario Fernando, Fernández-Contreras María Encarnación, Moreno Ana Laura Capote, Martín Irene Domínguez, Herráez Belén, Gamallo Carlos
Department of Oral & Maxillofacial Surgery, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
Ann Surg Oncol. 2009 Aug;16(8):2351-8. doi: 10.1245/s10434-009-0503-8. Epub 2009 May 16.
Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular responses to hypoxia and presumably plays a central role in the control of tumor growth. Polymorphisms or mutations increasing its activity and stability in vitro under normoxia have recently been identified. In this study, we aimed to investigate the effect of C1772T and G1790A single nucleotide polymorphisms (SNPs), located within the exon 12 of HIF-1alpha on the prognosis of early stages of oral squamous cell carcinoma (OSCC).
The frequency of C1772T and G1790A polymorphisms was determined by PCR-RFLP in 139 DNA samples from healthy volunteers and 74 patients with surgically treated T1/2 N0 OSCC. The impact of HIF-1alpha SNPs on tumor size, invasive depth, pathological features, and histological grade was studied. Correlations between genotype and relapse and/or disease-specific survival were evaluated by Kaplan-Meier analysis and log-rank test.
Concerning G1790A SNP, the frequencies of GA heterozygous and AA variant homozygous genotypes were significantly higher in patients than in healthy volunteers (32.8% vs. 6.5% and 4.7% vs. none, respectively) (P < .0001). Also, the presence of the variant allele A was associated to disease-relapse (P = .02) and shorter disease-free survival (P = .04). The genotype distribution of C1772T did not diverge between patients and healthy subjects, and no differences were observed with respect to disease-free or overall survival.
Our results suggest that G1790A polymorphism in the HIF-1alpha gene might confer susceptibility to OSCC and could be a marker of disfavorable prognosis at early stages.
缺氧诱导因子-1（HIF-1）是细胞对缺氧反应的关键调节因子，可能在肿瘤生长控制中起核心作用。最近已鉴定出在常氧条件下体外增加其活性和稳定性的多态性或突变。在本研究中，我们旨在调查位于HIF-1α第12外显子内的C1772T和G1790A单核苷酸多态性（SNP）对口腔鳞状细胞癌（OSCC）早期预后的影响。
通过PCR-RFLP测定139份健康志愿者DNA样本和74例接受手术治疗的T1/2 N0 OSCC患者中C1772T和G1790A多态性的频率。研究了HIF-1α SNP对肿瘤大小、浸润深度、病理特征和组织学分级的影响。通过Kaplan-Meier分析和对数秩检验评估基因型与复发和/或疾病特异性生存之间的相关性。
关于G1790A SNP，患者中GA杂合子和AA变异纯合子基因型的频率显著高于健康志愿者（分别为32.8%对6.5%和4.7%对无）（P <.0001）。此外，变异等位基因A的存在与疾病复发（P =.02）和无病生存期缩短（P =.04）相关。C1772T的基因型分布在患者和健康受试者之间没有差异，在无病生存期或总生存期方面也未观察到差异。
我们的结果表明，HIF-1α基因中的G1790A多态性可能使个体易患OSCC，并且可能是早期不良预后的标志物。
