Membralin基因rs1058810位点单核苷酸多态性与胃癌风险及预后研究

Association of single nucleotide polymorphisms of membralin with gastric cancer susceptibility and prognosis

目的研究membralin单核苷酸多态性(SNPs)与胃癌发生风险的遗传易感性及预后的相关性。方法收集我院508例原发性胃癌和对照组474例健康体检者外周血,membralin基因SNP位点rs1058810采用PCR-LDR检测其多态性、卡方及趋势卡方分析基因型与临床病理特征的关系,以及Kaplan-Meier分析与胃癌患者预后的关系。结果病例组rs1058810基因型AA、AC和CC频率(7.5%、40.0%、52.5%),等位基因A、C携带率(27.5%、72.5%),与对照组比较存在(C→A)多态性有显著统计学意义(P<0.05)。病例组基因型(AA和AC)与CC基因型比较显著增加胃癌的发生风险(OR_(adj)=5.0,95%CI=2.4~4.3,P<0.001;OR_(adj)=2.8,95%CI=2.0~3.8,P<0.001)。与临床病理参数相关性分析显示rs1058810位点基因型分布与肿瘤发生部位、浸润深度及淋巴结转移有统计学意义(P<0.05)。且基因型(AC/AA)突变率从远端(胃窦幽门)到近端(贲门)(P_(trend)=0.004)和从无到有淋巴结转移(P_(trend)=0.011)逐渐升高。结论membralin基因SNP位点rs1058810与胃癌的易感性相关,其基因型(AC/AA)在近端型及有淋巴结转移的胃癌突变率更高,提示更差的预后。

Objective To investigate the correlation of single nucleotide polymorphisms(SNPs)of the gene membralin with the genetic susceptibility and prognosis of gastric cancer.Methods Stomach tissue samples of 508 patients with primary gastric cancer and peripheral blood of 474 healthy people were collected.rs1058810,the SNP gene locus of membralin,which was screened in studies,were analyzed by PCR-LDR detection of the polymorphism and logistic regression analysis was used to evaluate their prognosis in gastric cancer patients.Results The frequency of AA,AC and CC genotype(7.5%,40.0%,52.5%)and allele A,C(27.5%,72.5%)in rs1058810 in the case group were significantly higher than the control group(P<0.05).The genotype(AA and AC)in the case group significantly increased the risk of gastric cancer(O_(Radj)=5.0,95%CI=2.4~4.3,P<0.001;O_(Radj)=2.8,95%CI=2.0~3.8%,P<0.001).The correlation analysis with clinicopathological parameters showed that rs1058810 genotype distribution was statistically significant with tumor location,invasion depth and lymph node metastasis(P<0.05).The mutation rate of genotype(AC/AA)increased from distal(antrum and antral pylorus)to proximal(cardia)(P=0.004)and from scratch to lymph node metastasis(P=0.011)gradually.Conclusion Membralin gene SNP locus rs1058810 is associated with susceptibility to gastric cancer,and its genotype(AC/AA)has a higher mutation rate in proximal and lymph node metastases,which implies relatively unfavorable prognosis.