Polymorphism of Promoter Region of TNFRSF1A Gene (-610 T > G) as a Novel Predictive Factor for Radiotherapy Induced Oral Mucositis in HNC Patients

Every year, about 650 thousand new cases of Head and Neck Cancer (HNC) are diagnosed globally. Apart from surgery, radiotherapy (RTH), chemotherapy (CHT) or its combination is used in the treatment of HNC. One of the most frequent complications and, at the same time, limitations of RTH is oral mucositis (OM). Proinflammatory cytokines (including TNF-alpha) play a key role in the development of OM. Genetic alterations, i.e. single nucleotide polymorphisms (SNPs) within genes encoding for receptors for TNF (ie. TNFRSF1A) may change their function. The aim of this study was to investigate relationship between a polymorphism of TNFRSF1A and occurrence and severity of acute reaction after RTH for HNC patients. Data from 58 HNC patients (stages I-IV) were analyzed. All of them were irradiated using IMRT technique with doses 50-70Gy. Oral mucositis (OM) was evaluated according to RTOG/EORTC guidelines. DNA from HNC patients were isolated from whole blood and genotypes were determined by sequencing method. Patients with TT or GT genotype demonstrated higher risk of manifestation of grade 3 OM in 5th week of RTH (p=0.041; OR=9.240; 95% CI: 1.101-77.581) compared to GG carriers. Similarly, high risk of grade 3 OM in patients with T allele presence was noted in 6th week (p=0.030; OR=10.50; 95%CI:1.257-87.690) and in 7th week (p=0.008; OR=5.625; 95% CI: 1.584-19.975) of treatment compared to patients with GG homozygote. Our results indicate an association between SNP of TNFRSF1A (rs4149570) gene and risk of more severe OM related to radiation therapy for HNC patients.