Epidemiological Characteristics Of The Common Single Nucleotide Polymorphism Of Hypoxia-inducible Factor-1α Gene And Its Influence On Angiogenesis And Clinicopathological Features Of Human Esophageal Squamous Cell Cancer

Background and objects: Angiogenesis is one of the most important molecular events in solid tumor growth and development, among which HIF-1 is a key regulator and plays an important role. Study had shown that SNP (C1772T) of HIF-1α gene exerts a lot of impacts on phenotypes of human head and neck squamous cell carcinoma(HHNSC) and renal cell carcinoma(RCC). But genotype distributions and the influence of C1772T of HIF-1α gene on clinicopathological features and angiogenesis of human esophageal squamous cell carcinoma (ESCC) remain unknown, which are the main objects of our study.Materials and methods: DNA genome of 95cases of ESCC and 104 healthy controls were extracted from peripheral blood. Genotypes of C1772T of 95 cases of ESCC patients and 104 healthy controls were studied by PCR-RFLP. Mutation was confirmed by direct DNA sequencing. The expressions of HIF-1α , CD34, VEGF were determined immunohistochemmically in paraffin-embedded specimens of 17 cases ofESCC. The influence of C1772T on tumor size, invasive depth, lymph node metastasis, distant metastasis, histological grade and TNM stage of ESCC was also studied.Results: The genotype frequencies observed in the ESCC patients and controls were 89.42%(93/104) versus 88.42%(11/95) for genotype C/C, and 10.58%(l1/104) versus 11.58%(84/95) for genotype C/T. T/T gonotype was not found in this study. The genotype distributions among both controls and ESCC patients showed a good agreement with Hardy-Weinberg equilibrium. No significant differences were documented for C1772T genotype distributions between the two groups (x~2=0.051 P=0.822). Larger tumors and higher lymph node metastasis rate were found in C/T group. Overexpression of VEGF and enhanced angiogenesis were observed in C/T group ESCC patients. Conclusions: Although there is no significant difference of genotype distribution of C1772T between ESCC patients and healthy controls, genotype C/T is associated with larger tumor and higher lymph node metastasis rate, and enhanced angiogenesis as well.