Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: Association with genetic polymorphism in DNA DSB repair genes

Abstract

Purpose: The aim of this study was to investigate the association between polymorphic variants of DNA repair genes with the susceptibility of acute oral mucositis (OM) in nasopharyngeal carcinoma (NPC) patients treated with radiotherapy.

Materials and methods: The study population consisted of 120 NPC patients treated with intensity-modulated radiation therapy (IMRT). Among them 70 patients also received concurrent chemotherapy. Genotypes in DNA repair genes Ku70 c.-1310C>G (rs2267437), Ku70 c.1781G> T (rs132788), Ku80 c.2099–2408G> A (rs3835), Ku80 c.*841G> A (rs2440) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) c.2888 + 713C> T (rs2213178) were determined by polymerase chain reaction combined with the restriction fragment length polymorphism (PCR-RFLP) technique. Mucositis was scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into the CTC0–2 group (CTC toxicity grade 0, 1 and 2) and the CTC3 + group (CTC toxicity grade 3 and above). Odd ratios (OR) and 95% confidence intervals (CI) were calculated using the multivariate logistic regression analysis.

Results: A significant difference in Ku70 c.1781G> T genotype distribution was observed between the CTC0–2 and CTC3 + groups for the 120 patients analyzed. The GG carriers were at higher risks for severe OM (CTC3+) compared with the TT homozygotes (OR = 3.000, 95% CI = 1.287–6.994, p = 0.011). No association was found between Ku70 (c.-1310C> G), Ku80 (c.2099–2408G> A, c.*841G> A), DNA-PKcs (c.2888 + 713 C > T) and the development of severe oral mucositis. Stratification analyses for the 50 patients treated with radiation alone further confirmed the association between the variant genotype of GG and severe OM (OR = 5.128, 95% CI = 1.183–22.238, p = 0.029). Concurrent radiochemotherapy increased the risk of severe OM for both the TT homozygotes and GG genotypes.

Conclusions: Our study suggests that the Ku70 c.1781G> T polymorphism may be a susceptibility factor for radiation-induced oral mucositis in Chinese nasopharyngeal carcinoma patients.

Keywords::

• Nasopharyngeal carcinoma
• radiation therapy
• oral mucositis
• polymorphism
• DNA repair

Acknowledgments

We would like to thank M. Dassarath of Department of Oncology, Queen Victoria Hospital, Candos, Quatre-Bornes, Mauritius, for her critical reading of the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by grants from the National Natural Science Foundation of China (No. 81372712 and 30900383) and Doctoral Fund for Youth Scholars of Ministry of Education of China (No. 20090142120051).