The relationship between TNF-α gene promoter polymorphism (− 1211 T > C), the plasma concentration of TNF-α, and risk of oral mucositis and shortening of overall survival in patients subjected to intensity-modulated radiation therapy due to head and neck cancer

Abstract

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-α) is a cytokine secreted during inflammatory process accompanying RTH and the development of cancer itself. Single nucleotide polymorphism (SNP) of the TNF-α 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-α 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-α (− 1211 T > C) have higher TNF-α 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-α 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-α plasma concentration and CC genotype of TNF-α are related to the higher risk of more severe OM in patients irradiated due to HNC. High TNF-α plasma concentration and CC genotype of TNF-α are independent prognostic factors for patients subjected to RTH due to HNC.

Associations of the -238(G/A) and -308(G/A) TNF-α Promoter Polymorphisms and TNF-α Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to Helicobacter pylori Infection in a Moroccan Population

“…The sTNF-α is detected at low doses in the serum of healthy subjects, while high levels are detected in patients suffering from cancer and inflammatory diseases (Erturk et al, 2016;Mlak et al, 2020;Morningstar-Wright, 2018;Mourtzikou et al, 2014;Stanilov et al, 2014). Decreases in TNF-α serum levels in patients receiving chemotherapy have been reported by many studies (Berberoglu et al, 2004).…”

Polymorphism of TNFRSF1 A may act as a predictor of severe radiation-induced oral mucositis and a prognosis factor in patients with head and neck cancer

“…We also found that TNF-a levels and the presence of the CC genotype are important prognostic factors in patients with HNC treated with RT. 24 Considering our previous and current studies related to the TNFÀTNFR axis, SNPÀ610 T> G seems to have a high predictive value for severe OM. It allows for prediction of onset of severe OM at the end of treatment (weeks 5À7 of RT).…”

“…[18][19][20]27,41 To the best of our knowledge, 2 of our previous publications were the first reports on the relationship between genetic alterations in the TNF-aÀTNFR axis and OM severity in patients undergoing RT. 23,24 Our previous study, which included a group of 58 patients with HNC treated with IMRT, showed a higher risk of grade 3 OM (in weeks 5, 6, and 7 of treatment) in patients with the T-allele of the TNFRSF1 A gene (À610 T > G, rs4149570). 23 Also, our recent investigation revealed that people with the CC genotype of the TNF-a gene (À1211 T>C) have a higher TNF-a blood concentration compared with those with a T allele.…”

“…The study was conducted in a population of patients who, to a limited extent, had already been included and described in some of our studies. 23,24 The decisive inclusion criteria were age greater than 18 years and a diagnosis of head or neck cancer. In addition, only patients who received a total radiation dose and treated with intensity modulation radiotherapy (IMRT) after surgery or as the final treatment method, with or without sequential and/or concomitant chemotherapy, were included in the study.…”

“…Besides, there is a certain methodologic difference between the 2 studies (in the case of À610 T>G, it was sequencing, and in the case of À135 T>C, it was specific Taqman probes), which could affect sensitivity in the detection of SNPs. 22,24 A meta-analysis conducted by Song et al (17 studies: 656 patients and 2193 controls) showed a significant correlation between the wild-type variant of the XRCC3 (x-ray repair crosscomplementing 3) gene (722 C>T, P.Thr241 Met, rs861539) and acute irradiation response in patients with various cancers. Of note, in the subgroup of patients with HNC, this SNP was significantly associated with a higher risk of adverse effects caused by radiation.…”