TGF-β1基因多态性与中晚期鼻咽癌患者放射性皮肤、口腔黏膜损伤的相关性研究  

Association of TGF-β1 Gene Polymorphisms and Radiation Skin and Oral Mucosa Injury in Patients with Na-sopharyngeal Carcinoma

作　　者：张静[1] 魏瑞[1] 

机构地区：[1]中南大学湘雅医院,湖南长沙410008

出　　处：《医学临床研究》2015年第4期642-646,共5页Journal of Clinical Research

基　　金：湖南省科技厅科技计划项目（2012FJ4321）

摘　　要：【目的】研究血清转化生长因子β1（TGF‐β1）基因的－509C／T和869T／C位点基因多态性与鼻咽癌患者放疗后急性放射性皮肤和口腔黏膜损伤的相关性。【方法】招募和随访本院收治的79例原发性中晚期鼻咽癌患者，采用鼻咽癌2008分期标准对肿瘤进行临床分期，所有患者均接受6M VX直线加速器根治性放疗。收集患者的临床资料和随访资料，抽取患者2 mL静脉血，提取基因组DNA ，用PCR和Sanger测序法对 TGF‐β1基因的－509C／T和869T／C位点进行分型。【结果】本研究共招募53例Ⅲ期鼻咽癌患者，26例Ⅵ期鼻咽癌患者，除了T分期和N分期外，其他基本临床资料无统计学差异。放疗后，Ⅲ期和Ⅳ期患者中重度皮肤和口腔黏膜损伤的发生率无显著性差异（ P ＞0．05）。通过分析发现 T G F‐β1基因的－509C／T和869 T／C位点突变与放射性皮肤损伤程度显著相关，－509 T等位基因携带者发生中重度（3～4度）皮肤损伤的风险显著高于CC基因型患者[ P ＝0．037；OR（95％ CI）＝3．314（1．19～9．22）]；869T／C位点中TC／CC基因型患者发生中重度皮肤损伤的风险较TT基因型患者显著增加[ P＝0．034，OR（95％ CI）＝2．86（1．11～7．37）]。同时发现869T／C位点突变与口腔黏膜损伤显著性关联，CC基因型患者发生口腔黏膜损伤的风险较TT基因型患者显著增加[ P ＝0．049，OR（95％ CI）＝5．33（1．03～27．53）]。【结论】TGF‐β1基因的－509C／T和869T／C位点基因多态性与鼻咽癌患者放疗后发生放射性皮肤和口腔黏膜损伤相关，该基因突变可能作为后期预测鼻咽癌个体化放疗不良反应评价的预测指标。[Objective] To explore the relationship between the polymorphisms of transforming growth factor beta 1 （TGF‐β1） gene and radiation skin and oral mucosa injury in patients with nasopharyngeal carcinoma （NPC） .[Methods] A total of 79 primary middle/advanced NPC patients on radiotherapy were recruited and followed up .The stage of disease was classified according to the 2008 NPC staging scheme .The baseline clinical and follow‐up data for each patient were collected by telephone counseling or outpatient services .Two milliliter peripheral blood was obtained before treatment for extracting genome DNA .Polymerase chain reaction （PCR） and Sanger sequencing were used to detect the mutated genotypes of -509C/T and 869T/C .Radiation skin damage was evaluated by the RTOG standard .The phenotypes had four grades of Ⅰ～ Ⅳ .And the radiation oral mucosa damage was classified into Ⅰ～ Ⅳ degrees by the WHO classification standard .Statistical analyses were conducted with SPSS13 .0 software .[Results] The grades of NPC wereⅢ （ n=53） and Ⅳ （ n=26） .All baseline clinical characteristics had no significant differences except for T and N classifications ,as well as the rate of radiation skin or oral adverse reactions （both P〉0 .05） .After the compare the rates of genotypes of different degrees of radiation adverse effects ,we found that the TGF‐β1 -509TT genotype was much higher in moderate or severe skin adverse reactions than CC genotypes [ P=0 .037 ,OR（95% ）=3 .314（1 .19～9 .22）] .Meanwhile ,the polymorphism of -509C/T was significantly associated with radiation skin adverse reactions [ P=0 .034 ,OR （95% ）=2 .86（1 .11～7 .37）] .Also 869T/C polymorphism had a significant association with radiation oral mucosa damage .And CC genotype carriers had a higher risk of serious oral mucosa damage than TT carriers （ P=0 .049） .[Conclusion]The -509C/T and 869T/C polymorphisms are significantly correlated with radiation skin damage after radiotherapy .And these gene mutati

关 键 词：转化生长因子β1/遗传学 多态现象 遗传 鼻咽肿瘤/放射疗法 放射性皮炎 口腔黏膜/损伤 

分 类 号：R739.63[医药卫生—肿瘤]