Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: Association with genetic polymorphism in DNA DSB repair genes
Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: Association with genetic polymorphism in DNA DSB repair genes
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鼻咽癌放疗患者急性口腔粘膜炎：与DNA DSB修复基因多态性的关联
DOI：
10.3109/09553002.2014.873558
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发表时间：
2014-03-01
影响因子：
2.6
通讯作者：
Ma, C-M Charlie
中科院分区：
文献类型：
--
作者：
Ren, Jing-Hua;Dai, Xiao-Fang;Ma, C-M Charlie
摘要目的：本研究旨在探讨DNA修复基因多态性与鼻咽癌放疗患者急性口腔黏膜炎易感性的关系。材料与方法：研究人群包括120例接受调强放射治疗（IMRT）的鼻咽癌患者。其中70例同时接受化疗。DNA修复基因Ku 70 c.- 1310C>G（rs2267437）、Ku70 c.1781G> T（rs132788）、Ku80 c.2099-2408G> A（rs3835）、Ku80 c.*采用聚合酶链反应结合限制性片段长度多态性（PCR-RFLP）技术检测了841 G> A（rs 2440）和DNA依赖性蛋白激酶催化亚基（DNA-PKcs）c.2888 + 713 C> T（rs 2213178）。使用不良事件通用术语标准（CTC）v.3.0量表对粘膜炎进行评分。将人群分为CTC 0 -2组（CTC毒性等级0、1和2）和CTC 3+组（CTC毒性等级3及以上）。采用多因素Logistic回归分析计算比值比（OR）和95%可信区间（CI）。结果如下：在所分析的120名患者中，在CTC 0 -2和CTC 3+组之间观察到Ku 70 c.1781G> T基因型分布的显著差异。与TT纯合子相比，GG携带者发生严重OM（CTC 3+）的风险更高（OR = 3.000，95%CI = 1.287-6.994，p = 0.011）。Ku70（c.- 1310C> G）、Ku80（c.2099-2408G> A，c. 841 G> A）、DNA-PKcs（c.2888 + 713 C > T）和严重口腔粘膜炎的发展。对50例单纯放疗患者的分层分析进一步证实了GG变异基因型与重度OM之间的相关性（OR = 5.128，95%CI = 1.183-22.238，p = 0.029）。同时放化疗增加了TT纯合子和GG基因型的严重OM的风险。结论：Ku 70 c.1781G> T多态性可能是鼻咽癌患者放射性口腔黏膜炎的易感因素。
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.