胃癌与肿瘤坏死因子相关凋亡诱导配体基因多态性及单倍型的关系  

Associations of genetic polymorphisms and haplotypes of tumor necrosis factor-related apoptosis inducing ligand with gastric cancer

作　　者：林秀清[1] 邵晓晓[2] 闵小彦[2] 胡定元[2] 夏盛隆[2] 俞俐琴[2] 蒋益[2] 

机构地区：[1]温州医学院附属第一医院消化内科,325000 [2]温州医学院附属第二医院消化内科

出　　处：《中华实验外科杂志》2013年第9期1961-1964,共4页Chinese Journal of Experimental Surgery

基　　金：浙江省卫生厅资助项目（2012KYA132）;温州市科技局资助项目（Y20080110）

摘　　要：目的 探讨胃癌与肿瘤坏死因子相关凋亡诱导配体（TRAIL）基因多态性及单倍型的关系.方法 收集321例胃癌患者及816例健康对照者,采用直接测序法检测TRAIL 3’非编码区（G1525A/C1595T）基因多态性,并行单倍型分析.结果 与正常对照组比较,胃癌组中TRAILG1525A位点突变等位基因（A）和基因型（GA＋AA）明显降低[30.37％（195/642）比53.92％（880/1632）；46.42％（149/321）比77.70％（634/816）,P＜0.01]；且TRAIL C1595T位点突变等位基因（T）和基因型（CT＋TT）亦显著降低[31.15％ （200/642）比55.39％（904/1632）；44.24％（142/321）比78.80％（643/816）,P＜0.01].单倍型分析发现TRAIL（G1525A/C1595T）2个位点之间完全连锁,胃癌患者组中GT单倍型频率显著高于对照组（9.98％比0.21％,P＜0.01）,而AT单倍型频率则明显低于对照组（42.45％比58.23％,P＜0.01）.进一步采用非条件Logistic回归分析发现TRAIL C1595T基因突变与胃癌患者的病理分期相关,Ⅲ期＋Ⅳ期胃癌患者中突变等位基因（T）和基因型（CT ＋TF）均显著高于Ⅰ期＋Ⅱ期胃癌患者[36.59％ （150/410）比21.55％ （50/232）;51.22％（105/205）比31.90％ （37/116）；P ＜0.01].结论 TRAIL （G1525A/C1595T）基因多态性及单倍型与胃癌相关.Objective To investigate the associations of genetic polymorphisms and haplotypes of tumor necrosis factor-related apoptosis inducing ligand （TRAIL） with gastric cancer.Methods A total of 321 patients with gastric cancer and 816 healthy controls were recruited in this study.The genetic polymorphisms of TRAIL （G1525A/C1595T） genes were detected by direct sequencing.A haplotype analysis was also performed on all study subjects.Results Frequencies of variant allele （A） and genotype （GA ＋ AA）in TRAIL G1525A were significantly lower in patients with gastric cancer than those in controls [30.37％ （195/642） vs.53.92％ （880/1632） ; 46.42％ （149/321） vs.77.70％ （634/816）,both P ＜ 0.01].The same results were obtained from variant allele （T） and genotype （CT ＋ TT） in TRAIL C1595T [31.15％ （200/642） vs.55.39％ （904/1632） ; 44.24％ （142/321） vs.78.80％ （643/816）,both P ＜0.01].The haplotype analysis showed that TRAIL G1525A and C1595T were in complete linkage disequilibrium.The GT haplotype in patients with gastric cancer was significantly higher than that in controls （9.98％ vs.0.21％,P ＜0.01）.However,the haplotype AT was significantly lower in patients with gastric cancer than in controls （42.45％ vs.58.23％,P ＜0.01）.Unconditional Logistic regression analysis revealed that the mutation of TRAIL C1595T was significantly related to the clinicopathological grading of patients with gastric cancer.Frequencies of variant allele （T） and genotype （CT ＋ TT） in TRAIL C1595T were significantly higher in patients with stage （Ⅲ ＋ Ⅳ） gastric cancer than in those with stage （Ⅰ ＋ Ⅱ）[36.59％ （150/410） vs.21.55％ （50/232） ; 51.22％ （105/205） vs.31.90％ （37/116） ; both P ＜0.01].Conclusion Genetic polymorphisms and haplotypes of TRAIL （G1525A/C1595T） are significantly correlated with gastric cancer.

关 键 词：胃癌 脱噬作用 肿瘤坏死因子相关凋亡诱导配体 基因多态性 

分 类 号：R735.2[医药卫生—肿瘤]