【作者】 赵洪云； 钟雪云； 陈运贤；

【Author】 Zhao Hong-Yun~1,Zhong Xue-Yun~2,Chen Yun-Xian~3,Jiang Wen-Qi~1,Guan Zhong-Zhen~1 1..Department of Oncology,Cancer Center,Sun Yat-Sen University,Guangzhou, Guangdong,510080,P.R.China; 2..Medical Hospital,Ji Nan University,Guangzhou,Guangdong,510630,P.R.China; 3 Department of Hematology,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,510060,P.R.China;

【机构】 中山大学肿瘤防治中心内科； 暨南大学医学院； 中山大学第一附属医院；

【摘要】 目的探讨肿瘤坏死因子α(Tumor necrosis factor alpha,TNFα)基因-308位和淋巴毒素(Lymphotoxin-α,LTα)基因+252位基因多态性与非霍奇金淋巴瘤(Non-Hodgkin’slymphoma,NHL)临床及预后的关系。方法用聚合酶链反应(PCR)、限制性内切酶消化及电泳技术,对96名NHL患者和72名正常对照者的TNFα和LTα基因的单碱基突变多态性进行检测,并收集病人组的临床资料,进行生存状况分析。结果1.NHL病人两位点联合单倍体分型在不同性别、年龄、分期、结外病变数、体能状态、B症状、血红蛋白、血白蛋白的分布没有显著性差异;比较单倍体分型与不同治疗反应却显示有显著性差别(NHL病人70.4%,正常人45.2%,p=0.018),治疗不敏感组中高危型比例明显大于敏感组,相对危险度为2.887(95%的置信区间为1.188～7.016)。2.用Kaplan-Meier方法进行生存分析,发现高危型与低危型的无病生存时间、总生存时间有显著性差异:高危型组平均生存时间为16.19个月,低危型组平均生存时间为48.63个月,在高危型组和低危型组,1年无病生存率为66.67%比87.5%(Logrank检验,P=0.0231);2年生存率为39.95%比65.13%,4年生存率8.32%比46.52%(Logrank检验,P=0.0012);用Cox回归模型显示TNF-308位和+252位联合单倍体状态分组对是影响预后的危险因素之一(P=0.034)。结论TNFα-308位和LTα+252位联合单倍体分型与中国广东地区NHL病人的治疗反应、生存等预后因素有关,可考虑将测定两位点多态性作为评估NHL预后的一种敏感指标。更多还原

【Abstract】 OBJECTIVE This study was designed to investigate the relationship between -308bp polymorphism in tumor necrosis factor-α(TNFα) gene and +252bp in lymphotoxin-α(LTα)gene and clinical course,outcome of NHL.METHODS The single base change polymorphism in TNFαgene and LTαgene were analyzed among 96 Chinese patients with NHL and 72 normal controls by using PCR-restrictive fragment length polymorphism(RFLP).The clinical data were collected and survival analysis was performed.RESULTS 1.In patients group, no statistically significant association was found between the presence of a given TNF/LT haplotype status and prognostic variables such as age,performance status,disease stage,B symptoms,the number of extranodal sites of disease,serum levels of lactate dehydrogenase(LDH), hemoglobin(Hb),albumin(Alb).The patients carrying low-risk haplotype achieved a more sensitive response to first-line therapy than the patients with high-risk haplotype(70.4%v 45.2%;P =0.018). 2.The estimated 1-year progression-free survival rates in the high-risk and low-risk groups were, respectively,66.67%versus 87.5%(log-rank test,P=.0231).The estimated 2-year and 4-year overall survival rates in the groups of patients carrying high-risk and low-risk haplotypes were, respectively,39.95%and 8.32%versus 65.13%and 46.52%(log-rank test,P=.0012) using Kaplan-Meier method.In multivariate Cox regression models the TNF/LT haplotype status was found to be one of risk factors for outcome(p=0.034).CONCLUSION There is a association of the TNF/LT haplotype status with response to therapy and outcomes of NHL in Canton area,China. Testing TNF/LT haplotype may become one sensitive method to evaluate the outcome.更多还原