碱基切除修复基因APE1,XRCC1多态性和肿瘤标志物CA199,CEA与鼻咽癌的临床关联研究

Association of DNA base-excision repair gene APE1,XRCC1 polymorphisms and tumor markers CA199,CEA with the clinical characteristics of nasopharyngeal carcinoma

目的:探讨人碱基切除修复基因APE1,XRCC1多态性和血清中肿瘤标志物CA199,CEA与鼻咽癌临床特征的相关性。方法:收集2008年1月至2012年9月期间,在成都军区总医院治疗的186例原发性鼻咽癌患者全血,并提取全血基因组DNA;记录其ID号、病理编号、性别、年龄、吸烟情况、发病部位、病理诊断等临床资料。对收集全血基因组DNA采用PCR-CTPP法来分析XRCC1(rs25487;Arg399Gln)和APE1(rs1130409;Asp148Glu)两种基因的基因多态性,采用蛋白芯片技术对CA199,CEA进行检测。数据比较用t检验与χ2分析,亚组分析用Logistic回归分析。P<0.05为差异有统计学意义。结果:CA199在发生远处转移的阳性率(18%)较未转移的高,但是无显著统计学差异(P=0.051)。CA199和CEA的阳性率与患者临床分期有显著差异(P值分别为0.047、0.037),但分期越高阳性率越低;在均值高低与临床分期的分析中,发现临床分期越晚,CA199和CEA的均值越高,CA199(t=-2.039;P=0.043);CEA(t=-2.317;P=0.022);发生远处转移的患者APE1突变频率为72.7%明显高于未发生转移者的突变频率62.8%,且差异有统计学差异(P<0.05);分期越晚APE1突变率越高,但P=0.081,差异无显著统计学差异。亚组分型Logistic回归分析结果;在XRCC1野生型中,性别为女性的分期较男性早(P=0.024;OR=0.286),我们认为在XRCC1野生型中,女性是一个保护性因素。结论:APE1,CEA、CA199与肿瘤分期相关,且APE1突变率与发生远处转移的关系密切,而分期越晚CEA与CA199的均值越高,XRCC1野生型是对于鼻咽癌女性患者是保护性因素。联合检测APE1、XRCC1、CEA和CA199对初诊的鼻咽癌患者的分期的预测有指导作用。由于本研究还存在样本量偏小、数据统计误差等客观因素,实验结果还需在以后的大量研究中进行验证。

Objective： To analyze polymorphisms of DNA BER genes（ APE1 and XRCC1） and tumor markers CA199,CEA;and explore their associations,and the combined effects of these variants,with the clinical characteristics of nasopharyngeal carcinoma.Methods： ID number,pathological number,gender,age,smoking status,parts and materials of pathological diagnosis of 186 cases of primary nasopharyngeal carcinoma patients treated in the Chengdu military command general hospital were collected during January2008 to September 2012 We detected SNPs of XRCC1（ Arg399Gln）,APE1（ Asp148Glu） using the polymerase chain reaction（ PCR）with peripheral blood samples from 186 patients with NPC and CA199,CEA tested by the protein chip. test and chi-square analysis were used,subgroup analysis using logistic regression analysis. Results： CA199 positive rate（ 18%） in the event of a distant metastasis was higher than the without metastasis,but there was no statistically significant difference（ P = 0. 051）,CA199 and CEA positive rate and clinical staging had significant difference（ 0. 047,0. 037,respectively）,but the higher stage hada lower positive rate. In the analysis between average and clinical staging,The CA199 and CEA had higher average in late clinical stage（ t =- 2. 039; P = 0. 043;t =- 2. 317; P = 0. 022,respectively）. The mutation frequency of APE1 with distant metastasis was significantly higher than that of without distant metastasis（ 72. 7% vs 62. 8%,P〈0. 05）. The female＇s stage was earlier than that of the male in the XRCC1 wild type（ P = 0. 024; OR = 0. 286）,so we speculated that female was a protective factor in the XRCC1 wild type. Conclusion： APE1,CEA,CA199 are associated with tumor stage,APE1 mutation rate being closely associated with occurrence of distant metastasis. The CA199 and CEA have higher average in late clinical stage; female is a protective factor in the XRCC1 wild type. Combined detection of APE1,XRCC1,CEA and CA199 staging in patients with nasopharyngeal carcinoma（ NPC） for both the prediction has a guiding role. Because there are small sample size,data statistical error and other objective factors in the study,the experimental results should be carried out in a number of studies.