肿瘤坏死因子基因多态性与非霍奇金淋巴瘤临床与预后的相关研究*

目的:探讨肿瘤坏死因子α（tumor necrosis factor alpha ，TNF-α）基因-308 位和淋巴毒素（Lymphotoxin-α ，LT α）基因+ 252 位基因多态性与非霍奇金淋巴瘤（NHL ）临床及预后的关系。方法:采用聚合酶链式反应（PCR ）、限制性内切酶消化及电泳技术，对中国广东省96例NHL 患者和72例正常对照者的TNF-α 和LT α 基因的单碱基突变多态性进行检测，收集其临床资料进行生存状况分析。结果:1）NHL 患者两位点联合单倍体分型在性别、年龄、分期等临床特征的分布无显著性差异；而联合单倍体分型的高危型在不同人群中有显著性差别（NHL 组70.4% ，对照组45.2% ，P=0.018），NHL 治疗不敏感组中高危型比例明显大于治疗敏感组，相对危险度为2.887（95%置信区间为1.188~7.016）。 2）Kaplan-Meier 方法进行生存分析，发现高危型与低危型的无瘤生存时间、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，1 年无瘤生存率分别为66.67% 、87.50%（P=0.023 1）；2 年生存率分别为39.95% 、65.13% ，4 年生存率分别为8.32% 、46.52%（P=0.001 2）；COX回归模型显示联合单倍体分型是影响预后的危险因素之一（P=0.034）。 结论:TNF-α-308 位和LT α + 252 位联合单倍体分型与中国广东省NHL 患者的治疗反应、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。 

Relationship of Tumor Necrosis Factor Genetic Polymorphisms with the Clinical Course and Outcome of Non-Hodgkin's Lymphoma

Objective:To investigate the relationship of-308bp polymorphism in tumor necrosis factor-α (TNFa)gene and+252bp in lymphotoxin-α(LTα)gene with the clinical course and outcome of non-Hodgkin's lymphoma(NHL).Methods:The single base change in TNFα gene and LTα gene was 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:In NHL patients,no statistcally significant association was found between the presence of a given TNF/LT haplotype status and clinical variables such as age,seX,disease stage,and so on.The patients carrying low-risk haplotype achieved a more sensitive response to first-line therapy than that in patients with high-risk haplotype(70.4%v 45.2%:P=0.018).The estimated 1-year progression-free survival rates in the high-risk and low-risk groups were 66.67% and 87.5%,respectively(log-rank test,P=0.0231).Kaplan-Meier method showed that the estimated 2-year and 4-year overall survival rates were 39.95%and 8.32%in patents carrying high-risk haplotypes and 65.13%and 46.52%in patients carrying low-risk haplotypes,respectively(log-rank test,P=0.0012).In multivariate Cox regression models.the TNF/LT haplotype status was found to be a dsk factor for outcome of NHL (P=0.034).Conclusion:There is an association between TNF/LT haplotype status and response to therapy and outcomes of NHL in Canton area,China.Detecting TNF/LT haplotype may be a sensitive method to evaluate the outcome of NHL.