2780 - The Association of Genetic Polymorphisms in the TNF-a Gene and Mucositis in Head and Neck Cancer Patients Treated with Combined Radiotherapy and Chemotherapy

R. Cavalieri¹, A. Rios², H. F. D. Oliveira³, and M. Kanashiro²; ¹Oncobeda - Centro Integrado de Oncologia de Campos, Campos, Brazil, ²Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Brazil, ³University of São Paulo, Ribeirão Preto, Brazil

Purpose/Objective(s): One of the main treatment modalities for head and neck cancer (HNC) is a combination of radiotherapy (RT) and chemotherapy (CT). Concomitant treatment with chemoradiation (CRT) is associated with mucositis. Recent studies have introduced the concept that mucosal damage is a multifactorial process, involving the genetic expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-a). Single nucleotide polymorphisms (SNPs) are alterations involving only one nucleotide, resulting in the exchange of a single DNA base pair. SNPs can affect protein synthesis, cell function and potentially increase the patients risk of developing more intense toxicity associated with treatment. The aim of our study was to assess the association between SNPs in the TNF-a gene and the severity of mucositis in CCP patients undergoing CRT. Materials/

Methods: To study the association between SNPs and mucositis, a molecular DNA analysis was performed on peripheral blood samples covering the entire promoter region and gene body of TNF-a (6150 bp region) in a cohort including 38 patients with CCP undergoing CRT. DNA was extracted and purified using the salt-out method. Genotyping was performed using the PCR method. A canonical discriminant analysis was carried out which included clinical, epidemiological and genetic variables.
Results: In the group of patients who developed grade I/II mucositis, 56.5% had PNS. Among those with grade III/IV mucositis, 54.5% had SNPs. SNP rs769177 was the most frequently found polymorphism. Canonical discriminant analysis combining all the groups of variables showed a significant relationship between the SNPs rs905841621, rs3093665, rs9282875, rs3093547 and the development of grade III and IV mucositis (p 0.006).
Conclusion: New SNPs were identified with potential relevance for predicting high-grade mucositis in the population studied. Further studies evaluating SNPs in the pro-inflammatory cytokine pathways are needed to establish their possible role as biomarkers in HNC.