线粒体DNA D-环区单核苷酸多态性与非霍奇金淋巴瘤患者预后的关系研究

Single Nucleotide Polymorphisms in the D-Loop Region of Mitochondrial DNA and Prognosis of Non-Hodgkin Lymphoma Patients

背景线粒体DNA(mt DNA)D-环区单核苷酸多态性(SNP)的积累可能与患癌风险和疾病预后有关。目的探讨mt DNA D-环区SNP与非霍奇金淋巴瘤(NHL)患者预后的关系。方法选取2000—2007年河北医科大学第四医院血液科接受治疗的NHL患者190例(NHL组),其中弥漫大B细胞淋巴瘤(DLBCL)108例(DLBCL亚组),T细胞淋巴瘤(TCL)82例(TCL亚组);同时收集体检健康者159例为对照组。记录NHL组患者性别、年龄、Ann Arbor分期、病理类型(B细胞型、T细胞型)、有无B症状、乳酸脱氢酶(LDH)水平、国际预后指数(IPI),检测NHL组与对照组mt DNA D-环区SNP。NHL患者预后采用多因素Cox比例风险回归模型进行分析。结果不同Ann Arbor分期、病理类型、有无B症状、不同LDH、IPI NHL患者5年生存率比较,差异均有统计学意义(P<0.05)。对照组与DLBCL亚组患者73、200、315位点等位基因频率比较,差异均有统计学意义(P<0.05)。对照组与TCL亚组患者73、16362、249、315位点等位基因频率比较,差异均有统计学意义(P<0.05)。不同146、199、309、315、16304位点等位基因频率NHL患者5年生存率比较,差异均有统计学意义(P<0.05)。多因素Cox比例风险回归模型结果显示,年龄〔HR=2.104,95%CI(1.095,4.403)〕、IPI〔HR=1.827,95%CI(1.098,3.034)〕、16304位点〔HR=0.523,95%CI(0.276,0.889)〕与NHL患者预后有回归关系(P<0.05)。结论 mt DNA D-环区SNP 16304位点与NHL患者预后相关,可通过检测mt DNA D-环区SNP 16304位点预测NHL患者预后。

Background Accumulation of single nucleotide polymorphisms（SNP） in the displacement loop（D-Loop） of mitochondrial DNA（mtDNA） might be associated with cancer risk and disease prognosis.Objective To discuss the relationship between the prognosis of non-Hodgkin lymphoma（NHL） patients and the SNP in D-Loop of mtDNA.Methods We enrolled 190 NHL patients（NHL group） who received treatment in Department of Hematology,Fourth Hospital of Hebei Medical University from 2000 to 2007,including 108 diagnosed with diffuse large B-cell lymphoma（DLBCL）,the DLBCL subgroup,and 82 with T-cell lymphoma（TCL）,the TCL subgroup.At the same time 159 healthy controls undergoing physical examination in the hospital during the same period were selected as the control group.The patient＇s gender,age,Ann Arbor staging,type of pathology（B-cell type,T-cell type）,B symptoms,lactate dehydrogenase（LDH） levels,and value of international prognostic index（IPI） in NHL group were recorded.The SNP in D-Loop of mtDNA in NHL group and control group were detected.The prognosis of NHL patients was analyzed by using a Cox proportional hazard regression model.Results The differences in 5-year survival rate among different Ann Arbor staging,type of pathology,B symptoms,LDH levels and value of IPI in NHL patients were statistically significant（P〈0.05）.The differences in 73,200 and 315 sites allele frequencies between the control group and the DLBCL subgroup were statistically significant（P〈0.05）.The differences in 73,16362,249,315 sites alleles frequencies between the control group and the TCL subgroup were statistically significant（P〈0.05）.The differences in 5-year survival rate among different 146,199,309,315 and 16304 sites allele frequencies in NHL patients were statistically significant（P〈0.05）.Multivariate Cox proportional hazards regression analysis showed that age（HR= 2.104,95%CI（1.095,4.403）],value of IPI（HR = 1.827,95%CI（1.098,3.034）],and 16304 site（HR= 0.523,95%CI（0.276,0.889）]were significantly associated with the prognosis of NHL patients（P〈0.05）.Conclusion The 16304 SNP site in D-Loop of mtDNA is associated with the prognosis of NHL patients,which can be used to predict the prognosis of NHL patients.