ENOSF1基因多态性预测结直肠癌患者卡培他滨治疗安全性  

Single nucleotide polymorphisms of ENOSF1 are predictors of therapeutic safety of capecitabine in colorectal cancer

作　　者：王鑫[1] 谢甲贝[2] 吴刚[3] 李修岭[2] 韩双印[2] 

机构地区：[1]新乡医学院研究生处,河南省新乡市453003 [2]河南省人民医院消化科,河南省郑州市450003 [3]河南省人民医院胃肠外科,河南省郑州市450003

出　　处：《世界华人消化杂志》2017年第35期3133-3140,共8页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81372405~~

摘　　要：目的评估烯醇酶超家族成员1(enolase superfamily member1,ENOSF1)基因多态性与卡培他滨治疗安全性的关系,探讨其预测价值.方法采集62例接受卡培他滨单药或联合治疗的结直肠癌患者外周静脉血,提取基因组DNA,检测ENOSF1基因单核苷酸多态位点rs2612091、IVS10-61C>T、IVS10-60G>A、rs1059394基因型;并对62例患者在接受卡培他滨治疗中出现的不良反应进行记录,比较不同基因型患者之间不良反应的差异.结果根据不良反应级别分为0-1级和2-4级两组,基因型采用两种分类方式,显性模型和隐性模型.显性模型中,IVS10-60G>A GG型发生2-4级手足综合征的风险明显高于AG/AA型,差异有统计学意义(χ~2=5.421,P=0.020,OR=4.364,95%CI:1.217-15.641);隐性模型中,IVS10-61C>T TT型发生2-4级腹泻的风险明显高于CT/CC型,差异有统计学意义(Fisher精确概率:P=0.039,OR=0.108,95%CI:0.015-0.788).结论 ENOSF1基因IVS10-61C>T与IVS10-60G>A位点有望作为遗传标志物,预测卡培他滨治疗的安全性.AIM To evaluate the relationship between single nucleotide polymorphisms of enolase superfamily member 1（ENOSF1） and capecitabine related toxic reactions.METHODS Peripheral venous blood was collected from 62 patients with colorectal cancer who were treated with capecitabine alone or combined with chemotherapy.Genomic DNA was extracted from the peripheral venous blood to genotype ENOSF1 single nucleotide polymorphisms rs2612091, IVS10-61 CT, IVS10-60 GA, and rs1059394 by sequencing. The toxic reactions of capecitabine were recorded, and their relationship with different genotypes was compared.RESULTS According to the level of toxic reactions, the patients were divided into two groups： patients with grade 0-1 toxicities and those with grade 2-4 toxicities. ENOSF1 genotypes were divided into a dominant model and a recessive model. In the dominant model, the risk of grade 2-4 hand-foot syndrome in patients with IVS10-60 GA GG genotype was significantly higher than that in patients with AG/AA genotype（χ~2 = 5.421, P =0.020, OR = 4.364, 95 % Cl： 1.217-15.641）. In the recessive model, the risk of grade 2-4 diarrhea in patients with IVS10-61 CT TT genotype was significantly higher than that in patients with CC/CT genotype（Fisher＇s exact test： P = 0.817, OR = 0.108, 95%CI： 0.015-0.788）.CONCLUSION The IVS10-61 CT and IVS10-60 GA loci of ENOSF1 gene are expected to be used as genetic markers to predict the therapeutic safety of capecitabine treatment.

关 键 词：卡培他滨 ENOSF1 基因多态性 结直肠癌 

分 类 号：R735.3[医药卫生—肿瘤]