摘要
目的:探讨肿瘤坏死因子α(tumornecrosisfactoralpha,TNF-α)基因-308位和淋巴毒素(Lvmphotoxin-α,LTα)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LTα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=0.0231);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=0.0012):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LTα+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。
Objective： To investigate the relationship of 308bp polymorphism in tumor necrosis factor-α （TNFα） 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 TNFa gene and LTa 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 statistically 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 patients carrying high-risk haplotypes and 65.13% and 46.52% in patients carrying low-risk haplotypes, respectively （log-rank test, P=-0.0012）. In multi- variate Cox regression models, the TNF/LT haplotype status was found to be a risk 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.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第1期23-28,共6页
Chinese Journal of Clinical Oncology
基金
广东省科技计划项目资助(编号:176053)
