Objective To detect the genetic variations of the tumor necrosis factor (TNF-α-308 G/A,rs1800629) and lymphotoxin-α (LTα + 252 A/G,rs909253) genes,and explore the association among TNF gene polymorphism,clinical characteristics and prognosis in childhood malignant lymphoma.Methods Malignant lymphoma patients diagnosed in Children's Hospital of Fudan University,Shanghai from July 2004 to July 2011 were enrolled in this study.DNA was extracted from peripheral blood samples.SNaPshot assay was used to detect the genotype.x2 test was used to analyze the association between the genetic variants and the clinical characteristics.Kaplan and Meier method was performed to estimate the event-free survival.Log-rank test was used to compare the differences among groups.Results Of the total 62 pediatric patients (17 females and 45 males),6 abandoned treatments after diagnosis and 2 were lost to follow up.The average age at diagnosis was 7.93 years old (ranged from 12 months to 14y7m).Among them,51 patients were diagnosed as non-Hodgkin lymphoma (15 females,36 males,with an average age of 7.25 years old),11 were diagnosed as Hodgkin disease (1 female,10 males,with an average age of 8.22 years old).TNF-α-308 and LTα +252 were in linkage disequilibrium.TNF1 and TNF2 were associated with LTα 10.5 (x2 =8.0756,P =0.0045) and LTα 5.5 (x2 =4.0678,P =0.045),respectively.We defined the carrier state of ≥ 2 TNF2 or LTα 5.5 genotype as high-risk,and ＜ 2 TNF2 or LTα 5.5 genotype as low-risk.No differences of TNF carrier states in age,sex,type of lymphoma,stage at diagnosis and treatrnent outcome were found (P ＞0.05).The probability of event-free survival analysis revealed that the median survival time was 34 months in TNF high-risk group;the survival rates of most cases in low-risk group were longer than 0.5.The 5-year disease-free survival rate was 47％ in TNF high-risk group,which has significantly difference with that in low-risk group (75％) (Log-rank test,P =0.045).The 5-year disease-free survival rates of non-Hodgkin lymphoma in TNF high-risk and low-risk groups were 53.5％ and 71.4％,respectively (Log-rank test,P =0.288).Conclusions The carrier states of TNF-α-308 combined with LTα + 252 allele could be associated with the prognosis of childhood malignant lymphoma.%目的 利用SNaPshot SNP分型技术检测儿童淋巴瘤患者肿瘤坏死因子α(TNF-α)基因-308 G/A位点及淋巴毒素(LTα)基因+252 A/G位点的单核苷酸多态性(SNP),探讨TNF基因多态性与儿童淋巴瘤临床特征及预后的关系.方法 收集2004年7月-2011年7月在我院血液科确诊的儿童淋巴瘤患者血样,提取基因组DNA,用SNaPshot SNP分型技术检测TNF-α基因-308G/A位点及LTα基因+252 A/G位点的单核苷酸多态性,分析TNF-α/LTα基因多态性与淋巴瘤患儿的临床特征及预后的关系.结果 62例淋巴瘤患儿中,非霍奇淋巴瘤51例,霍奇金病11例,TNF-α-308位点与LTα+252位点基因存在遗传连锁不平衡现象.将含2个及以上TNF或LTα高产位点的基因型定义为高危型,少于2个高产位点的基因型定义为低危型.对56例随访治疗的淋巴瘤患儿以Kaplan-Meier方法进行生存分析,高危型组和低危型组5年无事件生存率(EFS)分别为47％、75％(Log-rank检验,P=0.045),差异有显著性；对51例非霍奇金淋巴瘤患儿分析,高危型组和低危型组的5年EFS分别为53.5％、71.4％(Log-rank检验,P=0.288),差异无显著性.结论 TNF-α-308位点和LTα+252位点多态性联合危险度分型可能与儿童淋巴瘤预后有关.
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