Polymorphisms in Radio-Responsive Genes and Its Association with Acute Toxicity among Head and Neck Cancer Patients

Goutham Hassan Venkatesh,Kamalesh Dattaram Mumbrekar,Satish Rao Bola Sadashiva,Vadhiraja Bejadi Manjunath,Hitendra Negi,Donald Jerard Fernandes,Krishna Sharan,Sourjya Banerjee,Jian Jian Li

doi:10.1371/journal.pone.0089079

Goutham Hassan Venkatesh, Kamalesh Dattaram Mumbrekar + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0089079

Copy DOI

Abstract

Cellular and molecular approaches are being explored to find a biomarker which can predict the development of radiation induced acute toxicity prior to radiation therapy. SNPs in radiation responsive genes may be considered as an approach to develop tools for finding the inherited basis of clinical radiosensitivity. The current study attempts to screen single nucleotide polymorphisms/deletions in DNA damage response, DNA repair, profibrotic cytokine as well as antioxidant response genes and its predictive potential with the normal tissue adverse reactions from 183 head and neck cancer patients undergoing platinum based chemoradiotherapy or radiotherapy alone. We analysed 22 polymorphisms in 17 genes having functional relevance to radiation response. Radiation therapy induced oral mucositis and skin erythema was considered as end point for clinical radiosensitivity. Direct correlation of heterozygous and mutant alleles with acute reactions as well as haplotype correlation revealed NBN variants to be of predictive significance in analysing oral mucositis prior to radiotherapy. In addition, genetic linkage disequilibrium existed in XRCC1 polymorphisms for >grade 2 oral mucositis and skin reaction indicating the complex inheritance pattern. The current study indicates an association for polymorphism in NBN with normal tissue radiosensitivity and further warrants the replication of such studies in a large set of samples.

Highlights

Precise radiation delivery methodologies have significantly improved tumor cure and survival rate owing to recent developments, it has been at the expense of significant increase in normal tissue toxicity
In head and neck cancer (HNC) patients, oral mucositis and skin erythema are the major complications during the course of chemoradiotherapy
(RTOG) criteria [12] and the association between genetic polymorphism and oral mucositis and skin reaction was evaluated for the increased risk of developing these normal tissue adverse reactions

Summary

Introduction

Precise radiation delivery methodologies have significantly improved tumor cure and survival rate owing to recent developments, it has been at the expense of significant increase in normal tissue toxicity. In head and neck cancer (HNC) patients, oral mucositis and skin erythema are the major complications during the course of chemoradiotherapy. It affects pain control and adequate treatment delivery, thereby leading to unanticipated radiotherapy (RT) breaks, compromising treatment efficacy [1]. Studies have been conducted to associate the polymorphism in selected candidate genes with clinically observed normal tissue adverse effects, its clinical applicability as biomarker/s is still questionable [8] [9]. (RTOG) criteria [12] and the association between genetic polymorphism and oral mucositis and skin reaction was evaluated for the increased risk of developing these normal tissue adverse reactions

Materials and Methods

Results

Discussion