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Polymorphisms in radio-responsive genes and its association with acute toxicity among head and neck cancer patients.

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.

SUBMITTER: Venkatesh GH

PROVIDER: S-EPMC3942321 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Polymorphisms in radio-responsive genes and its association with acute toxicity among head and neck cancer patients.

Venkatesh Goutham Hassan GH Manjunath Vadhiraja Bejadi VB Mumbrekar Kamalesh Dattaram KD Negi Hitendra H Fernandes Donald Jerard DJ Sharan Krishna K Banerjee Sourjya S Bola Sadashiva Satish Rao SR

PloS one 20140304 3

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 ...[more]

PMID: 24594932

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Project description:BackgroundThe present study was planned to investigate possible association of single nucleotide polymorphisms (SNPs) of nucleotide excision repair (NER) genes such as XPC, XPD, XPG with acute radiation induced toxicities such as skin reactions and oral mucositis in normal tissue from head and neck cancer (HNC) patients receiving radiotherapy. Methods: Two hundred and fifty HNC patients receiving radiotherapy were enrolled in this study and the acute toxicity reactions and radiation response were recorded. Association of SNPs rs2228001 of XPC, rs238406, rs13181 of XPD and rs17655 of XPG gene with normal tissue reactions in the form of dermatitis and mucositis were studied by PCR-RFLP and direct DNA sequencing.ResultsThe results of univariate analysis of SNPs of XPC, XPD and XPG showed that XPC polymorphism at codon 939 of exon 15 (A>C) was not associated with dermatitis (OR=0.30, 95% CI: 0.06-1.39; p=0.125), or oral mucositis (OR=1.14, 95% CI: 0.41-3.20; p=0.793). The XPD codon 156 of exon 6 (C>A) and codon 751 of exon-23 A>C) polymorphism showed no association with radiosensitivity in HNC patients (OR=1.50, 95% CI: 0.60-3.71; p=0.080) for dermatitis, (OR=1.54, 95% CI: 0.66-3.61; p=0.312) for oral mucositis. The 1104 Asp variant genotype or allele of XPG (OR=1.35 95% CI: 0.50-3.64; p=0.541) showed no association with degree of radiotherapy associated dermatitis or mucositis (OR=0.80, 95% CI: 0.32-2.03; p=0.648) in HNC patients. The variant C allele of 2920 A/C genotype of XPC gene at codon 939 of exon 15, found protective with developing skin reactions with grade >1 (OR=0.60, 95% CI: 0.36-0.97; p=0.039) in HNC patients treated with radiotherapy.ConclusionThe results obtained in this study concluded that the SNPs rs2228001of XPC, rs238406, rs13181 SNPs of XPD and rs17655 SNP of XPG are not associated with normal tissue toxicity in HNC patients treated with radiotherapy. Radiotherapy with high radiation dose was significantly associated with oral mucositis in response to radiotherapy.

Project description:BackgroundThe associations between RAD51 gene polymorphisms (G135C and G172T) and risk of head and neck cancer (HNC) have been investigated, but the results are controversial. The aim of this study was to provide a more precise estimation of its relationship with HNC using a meta-analysis.MethodsRelevant studies were retrieved from the PubMed, Excerpta Medica Database, and China National Knowledge Infrastructure. Strict selection and exclusion criteria were determined, and the odds ratio (OR) with a 95% confidence interval (CI) was used to assess the strength of the association between RAD51 polymorphisms and HNC risk.ResultsSix studies were eligible for RAD51 G135C (1593 cases and 1719 controls), and three studies were eligible for RAD51 G172T (997 cases and 979 controls). In the overall population, significant association between RAD51 G135C polymorphism and HNC risk was observed under allele model (C vs G: OR = 1.21, 95% CI = 1.04-1.41, P = 0.015). In the subgroup analysis by smoking status, a significant association was found among smokers (C vs G: OR = 1.59, 95% CI = 1.25-2.04; GC vs GG: OR = 2.29, 95% CI = 1.29-4.05; GC + CC vs GG: OR = 2.08, 95% CI = 1.56-2.78). When stratified based on drinking status, a significant association was found among drinkers(C vs G: OR = 1.60, 95% CI = 1.21-2.11; GC vs GG: OR = 2.50, 95% CI = 1.16-5.38; GC + CC vs GG: OR = 2.17,95% CI = 1.56-3.01). However, no significant association with HNC risk was demonstrated when stratified based on source of control and ethnicity. For G172T polymorphism, the results showed no significant risk association in overall analysis. In the subgroup analysis by ethnicity, the result suggested that a decreased HNC risk was found among Caucasians (T vs G: OR = 0.82, 95% CI = 0.72-0.95; TT vs GG: OR = 0.62, 95% CI = 0.46-0.84; TT vs GT + GG: OR = 0.64, 95% CI = 0.49-0.84).ConclusionThis meta-analysis suggested that RAD51 G135C is associated with increased HNC risk, especially among smokers and drinkers, while G172T polymorphism may play a protective role against HNC among Caucasians. Larger-scale and well-designed studies are needed to further clarify the association.

Dataset Information

Polymorphisms in radio-responsive genes and its association with acute toxicity among head and neck cancer patients.

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Polymorphisms in radio-responsive genes and its association with acute toxicity among head and neck cancer patients.

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