CYP1B1基因多态性与食管鳞状细胞癌易感性及预后关系的研究  

Association of CYP1B1 gene polymorphism with prognosis of esophageal squamous cell carcinoma

作　　者：刘月平[1] 张玲玲[1] 王顺平[2] 李洁[1] 安景辉 王小玲[1] 

机构地区：[1]河北医科大学第四医院病理科,河北石家庄050011 [2]河北医科大学第四医院内镜室,河北石家庄050011 [3]邢台市三院胸外科,河北邢台054000

出　　处：《中国现代医学杂志》2011年第33期4122-4127,共6页China Journal of Modern Medicine

基　　金：河北省自然科学基金资助项目(C2009001209);河北省卫生厅2009年医学科学研究重点课题计划(200930);河北省强势特色学科资助(200552)

摘　　要：目的探讨CYP1B1基因C432G及A453G两个多态性位点分布频率特征与食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)之间的相关性;分析其与临床病理指标及预后的关系。方法以河北医科大学第四医院2004年间120例有完整随访资料的ESCC患者术后石蜡包埋组织为研究对象,以120例内镜检查的食管正常组织标本作为对照组,酚氯仿法抽提基因组DNA,PCR-SSP法检测CYP1B1基因C432G及A453G两个多态性位点基因型分布频率,分析各基因型与ESCC患者临床病理特征及其发病风险的相关性。COX回归模型进行多因素生存分析,Kaplan-Meier生存曲线进行单因素生存分析,Log-Rank法比较各基因型5年生存率的差别。方法 CYP1B1A453G位点不具多态性;CYP1B1C432G基因CC、CG、GG基因型在ESCC患者组与对照组的分布频率分别为67.50%、18.33%、14.17%和74.17%、17.50%、8.33%,无明显统计学差异(P>0.05)。G等位基因携带者患病风险是CC基因型的1.477倍(OR=1.477,95%CI=0.942～2.317)。临床病理特征分析结果显示CYP1B1C432G基因CG、GG基因型在有淋巴结转移组和临床分期较晚组分布频率较高。Kaplan-Meier单变量分析结果表明CG+GG基因型患者5年生存率明显低于CC基因型患者。而COX模型多因素生存分析结果提示CYP1B1C432G基因多态性与ESCC5年生存率无关。结论食管癌组和对照组CYP1B1A453G等位基因多态性均为AA基因型,中国河北汉族人群此位点可能不存在多态性。C432G等位基因具有多态性。CYP1B1C432G基因多态性可能与增加ESCC的易感性无关联,但与ESCC患者是否有淋巴结转移和临床分期相关,CG+GG基因型可能是预测ESCC患者不良预后的辅助指标。[Objective] To investigate the relation of cytochrome P4501B1 （CYP1B1） gene polymorphisms （C432G and A453G） and esophageal squamous cellcarcinoma （ESCC） valuable reference for risk of ESCC; and to explore the correlation between CYP1B1 and clinieopathologic features, hoping to provide a new theoretic basis for predicting prognosis. [Methods] The frequencies of CYP1B1 C432G and CYP1B1 A453G polymorphisms were determined in120 patients, with primary esophageal carcinoma and 120 healthy individuals. Genomic DNA was extracted from the tumor and individual gene fragments were polymerase chain reaction amplified （PCR-amplified）. The polymorphisms were determined by sequence-specific primers （PCR-SSP）. PCR-SSP was used for the detection of CYP1B1 genotypes in 120 patients with ESCC and 120 controls. 120 patients of ESCC who underwent a curative resection, were studied by univariate and multivariate analysis of Kaplan-Meier survival analysis and Cox proportional hazard model. All data were analyzed by SPSS 13.0 for windows. [Results] The A453G polymorphism was AA genotype in allof cases and controls in Hebei province. The frequencies of CC, CG and GC, genotypes of C432G polymorphism were 67.50% and 74.17%, 18.33% and 17.50%, 14.17% and 8.33%, patients and controls, respectively. The frequency of the G allele was significandy higher in the ESCC patients than that in controls （X^-=2.907, P =0.088, OR=1.477, 95%CI： 0.942-2.317）. The position rates were found between the CYP1B1 C432G polymorphism and metastasis of lymph node group and the lower clinical stage. Kaplan-Meier survival analysis suggested that tumor differentiated degree, depth of tumor invasion, metastasis of lymph node, clinical stage and CYPIB1 C432G genotypes were eorrelated with the prognosis of ESCC （P 〉0.05）. But according to multivariate analysis of COX model, no significant correlations were found between the CYP1B1 C432G polymorphism with the prognosis of ESCC （iv 〉0.05）. [ Conclusion ] The A453G polymorphism was AA

关 键 词：食管癌 CYP1B1基因多态性 PCR-SSP 预后 

分 类 号：R361.2[医药卫生—病理学]