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

Abstract

The aim of this study was to evaluate the relationship between single nucleotide polymorphism (SNP) (À135 T>C) of TNFRSF1 A and the frequency of occurrence and severity of oral mucositis (OM) in patients with head and neck cancer (HNC) treated with radiotherapy (RT). Study Design. This retrospective, cohort study included 60 patients with HNC treated with intensity-modulated radiation therapy (IMRT). TNFRSF1 A SNP analysis (À135 T>C) was performed by using molecular probes (TaqMan, ThermoFisher Scientific, Waltham, MA) in DNA isolated from peripheral blood (QIAamp DNA MiniKit; Qiagen, Germantown, MD). Results. CC genotype was related to 4.5-fold higher risk of grade 2 OM after the second week of RT. Similarly, CC carriers had a significantly higher risk of severe (grade 3) OM after the fourth (6-fold) and fifth (7.5-fold) weeks of RT. The CC genotype of the TNFRSF1 A gene was significantly correlated with a higher risk of shorter overall survival (OS) (> 37 months follow-up period; hazard ratio [HR] = 2.78). Conclusions. SNP (À135 T>C) of the TNFRSF1 A gene may act as a predictor of OM occurrence in patients with HNC treated with IMRT. The studied SNP may also serve as a prognostic factor in such cases. (Oral Surg Oral Med Oral Pathol Oral Radiol 2020;130:283À291)

Single Nucleotide Polymorphisms as Biomarker Predictors of Oral Mucositis Severity in Head and Neck Cancer Patients Submitted to Combined Radiation Therapy and Chemotherapy: A Systematic Review

“…The TNF receptor, TNFR1, when activated, regulates an apoptotic pathway and may be involved in the development of mucositis. Two articles assessed SNPs in the promoter region of the gene encoding the receptor protein, TNFRSF1A, and showed a significant increase in the likelihood of grade 3 mucositis in the last weeks of RT in CC, TT, or GT genotype carriers [ 27 , 31 ]. The other article addressing the TNF pathway assessed the relationship between the SNP (-1211 T>C, rs1799964) in the TNF-α gene itself and the occurrence and intensity of OM [ 32 ].…”

“…In their work, Mlak et al (2020) showed that the CC genotype of the TNFRSF1 A gene is associated with a more severe course of OM [ 31 ]. The SNP identified in this study is located in the regulatory region of the TNFRSF1 A gene.…”

The Molecular Mechanism of Multiple Organ Dysfunction and Targeted Intervention of COVID-19 Based on Time-Order Transcriptomic Analysis

“…found that CSF1 overexpression after SARS-CoV-2 infection led to pulmonary fibrosis by promoting the recruitment and activation of macrophages ( 50 ). TNFRSF1A is a tumor necrosis factor receptor, and the interaction between tumor necrosis factor and TNFRSF1A plays an important role in inhibiting the occurrence of inflammation, tumor proliferation, migration, and invasion ( 52 ). Wilson et al.…”

“…Bertolazzi et al found that CSF1 overexpression after SARS-CoV-2 infection led to pulmonary fibrosis by promoting the recruitment and activation of macrophages (50). TNFRSF1A is a tumor necrosis factor receptor, and the interaction between tumor necrosis factor and TNFRSF1A plays an important role in inhibiting the occurrence of inflammation, tumor proliferation, migration, and invasion (52). Wilson et al found that TNFRSF1A induced alveolar epithelial cell dysfunction in the early stages of acute respiratory distress syndrome, which promotes lung permeability and inhibits the reabsorption of alveolar fluid (53).…”

Attempts to Understand Oral Mucositis in Head and Neck Cancer Patients Through Omics Studies

“…Five studies were conducted on a small number of HNSCC patients receiving radiation therapy in the oncology department at the Medical University of Lublin (Lublin, Poland). They showed that polymorphisms in GHRL (rs1629816) [40], TNFRS1A [41] (rs4149570, rs767455) [42]), TNFA (rs1799964) [43], and APEH (rs4855883) [44] were significantly associated with OM. In a larger sample (n = 114) of Chinese patients with HNSCC receiving radiotherapy, Chen et al [45] found the XRCC1 variant (rs25487) to be associated with an increased risk of OM.…”