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Open Access Research

SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

Ghazi Alsbeih14*, Medhat El-Sebaie2, Najla Al-Harbi1, Khaled Al-Hadyan1, Mohamed Shoukri3 and Nasser Al-Rajhi2

Author Affiliations

1 Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia

2 Radiation Oncology Section, Oncology Centre, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia

3 National Biotechnology Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia

4 Radiation Biology Section, Biomedical Physics Department, KFSHRC, MBC-03, P.O. Box 3354, Riyadh 11211, Saudi Arabia

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Radiation Oncology 2013, 8:125  doi:10.1186/1748-717X-8-125

Published: 22 May 2013

Abstract

Background

Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.

Methods

A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).

Results

Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.

Conclusions

Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy.

Keywords:
Single nucleotide polymorphism (SNP); Radiosensitivity; Late reactions to radiotherapy; Fibrosis; Follow up; Nasopharyngeal carcinoma