EDN1及EDNRA基因多态性与局部区域晚期鼻咽癌预后的关系  

Prognostic role of endothelin-1 and endothelin A receptor gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma

作　　者：温月凤[1] 齐斌[1] 莫浩元[1] 刘怀[1] 陈秋燕[1] 李娟[1] 叶艳芳[1] 郭翔[1] 麦海强[1] 

机构地区：[1]华南肿瘤学国家重点实验室中山大学肿瘤防治中心鼻咽科,广东广州510060

出　　处：《中华肿瘤防治杂志》2010年第18期1401-1406,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30600755);"863计划"子课题(2006AA02A404);广东省科委项目(2007B060401064);广东省医学科研基金(B2006063);广州市科委项目(2007Z1-E4022)

摘　　要：目的:探讨EDN1及EDNRA基因多态性与初治局部区域晚期鼻咽癌患者预后的关系。方法:采用LDR-PCR技术对203例鼻咽癌患者EDN1及EDNRA基因7个位点的基因多态性(SNP)进行检测,用Kaplan-Meier法进行生存分析,多因素分析采用Cox回归模型。结果:携带EDN-RA/H323H突变型杂合子TC基因型患者的5年无进展生存率(PFS)、总生存率(OS)、无远处转移生存率(DMFS)及无局部区域复发生存率均比携带纯合子CC+TT基因型的患者低,P<0.05;Cox模型多因素分析显示,EDNRA/H323HSNPs是影响局部晚期鼻咽癌患者PFS(HR:1.964;P=0.004)、OS(HR:1.955;P=0.009)、DMFS(HR:1.984;P=0.023)及LRFS(HR:2.112;P=0.036)的独立预后因素。携带EDNRA/G-231A突变基因型GA或AA患者的5年PFS和LRFS均低于携带野生型GG基因型患者(P<0.05),Cox模型多因素分析显示,EDNRA/G-231ASNPs是影响局部晚期鼻咽癌患者PFS(HR:1.826;P=0.017)及LRFS(HR:3.262;P=0.005)的独立预后因素。结论:EDNRA基因H323H、G-231ASNPs是影响局部区域晚期鼻咽癌的独立预后因素,为晚期鼻咽癌的预后判断及个体化治疗提供了新的分子指标。OBJECTIVE：To investigate the prognostic role of endothelin-1 and endothelin A receptor gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma （NPC）.METHODS：The single nucleotide polymorphisms （SNPs） in 7 sites of the endothelin-1 and endothelin A receptor gene were detected from 203 NPC patients by LDR-PCR technique,and Kaplan-Meier method was used to analyze the survival rate,and multivariate analysis was performed with Cox regression model.RESULTS：The 5-year progression free survival rate （PFS）,overall survival rate （OS）,distant metastasis-free survival rate （DMFS）,and locoregional relapse-free survival rate （LRFS） for the patients who carried EDNRA/H323H mutational heterozygote genotype TC were all lower than those who carried homozygote genotype CC and TT（P0.05）.Cox model multivariate analysis showed that EDNRA/H323H SNPs was an independent prognostic factor for patients with locoregionally advanced NPC,which affected PFS（HR：1.964;P=0.004）,OS （HR：1.955;P=0.009）,DMFS （HR：1.984;P=0.023） and LRFS （HR：2.112;P=0.036）.The 5-year PFS and LRFS for the patients who carried EDNRA/G-231A mutational GA and AA genotype were all lower than those who carried wild type GG genotype （P0.05）.Cox model multivariate analysis showed that EDNRA/G-231A SNPs was an independent prognostic factor for patients with locoregionally advanced NPC,which affected PFS（HR：1.826;P=0.017） and LRFS （HR：3.262; P=0.005）.CONCLUSION：EDNRA/H323H and EDNRA/G-231A SNPs are independent prognostic factors for patients with locoregionally advanced NPC,which provide new molecular indexes for advanced NPC patients＇ prognosis evaluation and individualized treatment.

关 键 词：鼻咽肿瘤 内皮素-1 内皮素受体A 基因 综合疗法 预后 

分 类 号：R739.63[医药卫生—肿瘤]