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. 2018 Jan;24(1):135-143.
doi: 10.1007/s12253-017-0227-1. Epub 2017 Apr 11.

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

Anna Brzozowska  1 , Tomasz Powrózek  2 , Iwona Homa-Mlak  2 , Radosław Mlak  2 , Marzanna Ciesielka  3 , Paweł Gołębiowski  4 , Teresa Małecka-Massalska  2
Affiliations

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

Anna Brzozowska et al. Pathol Oncol Res. 2018 Jan.

Abstract

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-α) 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.

Keywords: Head and neck cancer; Oral mucositis; Polymorphism; Radiotherapy; TNFRSF1A.

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Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

All persons gave their informed consent prior to their inclusion in the study.

Human and Animal Studies

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
An example of results of TNF receptor gene sequencing. Changes in the SNP (rs414141) were marked with a black box. Figure 1 a and b shows the GT heterozygous and GG homozygous patients respectively
See this image and copyright information in PMC

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