BACKGROUND: Genetic polymorphisms of vitamin D receptor gene (VDR) and genes involved in vitamin D metabolism pathway, CYP27B1 and CYP24B1, may affect individual susceptibility to oral squamous cell carcinoma. The purpose of this study was to evaluate the associations between VDR, CYP27B1 and CYP24A1 gene polymorphisms with oral cancer risk and survival. METHODS: Study cohort consisted of 110 patients with oral cancer and 122 healthy controls. The genotypes of the analysed genes were determined by PCR-RFLP or real-time PCR method. RESULTS: The significant decrease of oral cancer risk was observed in individuals with heterozygote genotype of CYP24A1 gene (rs2296241) (odds ratio 0.281, P = 0.000) in comparison with wild type. Patients with VDR FokI ff wild type genotype had significantly worse overall survival (P = 0.012, log rank) compared with heterozygous and mutated genotype combined. A stratified analysis by the lymph node involvement and tumour stage showed that ff is associated with poor survival in groups with and without lymph node involvement (P = 0.025, P = 0.040, respectively) and in stage III tumours (P = 0.026). Multivariate Cox's regression analysis revealed that VDR FokI could be considered an independent prognostic factor. CONCLUSION: Our findings indicate that CYP24A1 gene polymorphism might have an influence on the susceptibility to oral cancer. VDR FokI polymorphism was associated with worse survival and could be considered as an independent prognostic marker.
BACKGROUND: Genetic polymorphisms of vitamin D receptor gene (VDR) and genes involved in vitamin D metabolism pathway, CYP27B1 and CYP24B1, may affect individual susceptibility to oral squamous cell carcinoma. The purpose of this study was to evaluate the associations between VDR, CYP27B1 and CYP24A1 gene polymorphisms with oral cancer risk and survival. METHODS: Study cohort consisted of 110 patients with oral cancer and 122 healthy controls. The genotypes of the analysed genes were determined by PCR-RFLP or real-time PCR method. RESULTS: The significant decrease of oral cancer risk was observed in individuals with heterozygote genotype of CYP24A1 gene (rs2296241) (odds ratio 0.281, P = 0.000) in comparison with wild type. Patients with VDR FokI ff wild type genotype had significantly worse overall survival (P = 0.012, log rank) compared with heterozygous and mutated genotype combined. A stratified analysis by the lymph node involvement and tumour stage showed that ff is associated with poor survival in groups with and without lymph node involvement (P = 0.025, P = 0.040, respectively) and in stage III tumours (P = 0.026). Multivariate Cox's regression analysis revealed that VDR FokI could be considered an independent prognostic factor. CONCLUSION: Our findings indicate that CYP24A1 gene polymorphism might have an influence on the susceptibility to oral cancer. VDR FokI polymorphism was associated with worse survival and could be considered as an independent prognostic marker.
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