The relationship between TNF-alpha gene promoter polymorphism (- 1211 T > C), the plasma concentration of TNF-alpha, and risk of oral mucositis and shortening of overall survival in patients subjected to intensity-modulated radiation therapy due to head and neck cancer.
PURPOSE: Radiotherapy (RTH) usually combined with chemotherapy (C-RTH) is the main method of treatment in head and neck cancer (HNC). The most common complication of RTH is oral mucositis (OM). At a certain stage of RTH, it occurs in almost all patients, often lead to discontinuation of treatment. Tumour necrosis factor alpha (TNF-alpha) is a cytokine secreted during inflammatory process accompanying RTH and the development of cancer itself. Single nucleotide polymorphism (SNP) of the TNF-alpha promoter region can potentially affect the function or expression of this cytokine, and thus modulate the risk of occurrence and intensity of OM and shortening of overall survival (OS). METHODS: The study group consisted of 62 patients with HNC in whom intensity-modulated radiation therapy (IMRT) technique was applied. The plasma TNF-alpha level was assessed using the ELISA Kit. Genotyping was performed using a real-time PCR method. RESULTS: HNC patients with the CC genotype of TNF-alpha (- 1211 T > C) have higher TNF-alpha plasma concentrations than those with T allele (10.70 vs 9.62 ng/ml). Patients with the 3rd degree of OM have significantly higher TNF-alpha levels after 5th (10.40 vs 9.45 ng/ml) and 7th (10.32 vs 9.60 ng/ml) week of RTH. CC genotype was related to a higher risk of 3rd degree OM development in the last weeks of RTH (5th, OR = 7.33; 7th, OR = 23.15). CONCLUSIONS: High TNF-alpha plasma concentration and CC genotype of TNF-alpha are related to the higher risk of more severe OM in patients irradiated due to HNC. High TNF-alpha plasma concentration and CC genotype of TNF-alpha are independent prognostic factors for patients subjected to RTH due to HNC.
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