Polymorphisms in the hypoxia inducible factor 1-alpha and the impact on the prognosis of early stages of oral cancer.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Muñoz-Guerra
Mario Fernando
MF
Department of Oral & Maxillofacial Surgery, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain. maxmferm@excite.com
Fernández-Contreras
María Encarnación
ME
Moreno
Ana Laura Capote
AL
Martín
Irene Domínguez
ID
Herráez
Belén
B
Gamallo
Carlos
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit