E-钙黏蛋白基因多态性与上皮性卵巢癌发病风险关系的研究

目的 探讨E-钙黏蛋白基因(E-cadherin gene,CDH1)单核苷酸多态性(single nucleotide polymorphism,SN-P)与上皮性卵巢癌发病风险的关系.方法 采用聚合酶链反应-限制性片段长度多态性方法分析207例上皮性卵巢癌患者和256名健康对照的CDH1基因启动子区-160C/A、-347G/GA和3′UTR+54C/T3个SNP位点基因型频率分布;采用免疫组织化学方法检测携带3′UTR+54C/T SNP位点不同基因型的卵巢癌患者癌组织CDH1基因的表达情况.结果 CDH1基因-160C/A和-347G/GA 2个SNP位点的基因型和等位基因频率分布在患者组与健康对照组间差异无统计学意义(P＞0.05).3′UTR+54C/T SNP 位点的基因型与等位基因频率分布在患者与健康对照组间差异有统计学意义,患者组中CC基因型和C等位基因频率(65.2%,89.1%)明显高于对照组(52.7%,64.5%)(P＜0.01);CC基因型可能显著增加上皮性卵巢癌的发病风险(比值比为1.85,95%可信区间为1.27～2.69);且免疫组化研究表明CC基因型患者癌组织CDH1基因的表达明显低于T等位基因(CT+TT)携带者(P＜0.05).采用2LD软件分析显示-160C/A、-347G/GA两位点间存在连锁不平衡(D′=0.999 582),-160A/-347GA单倍型仅在患者组中检测到(5.1%),-160C/-347GA单倍型可能明显降低卵巢癌的发病风险(比值比为0.66,95%可信区间为0.45～0.96).结论 CDH1基因-160C/A、-347G/GA SNP可能与上皮性卵巢癌的发病风险无关,但两位点的单倍型可能改变上皮性卵巢癌的发病风险.3′UTR+54C/T多态CC基因型可能成为上皮性卵巢癌发病的潜在危险因素.

Association of three single nucleotide polymorphisms of the E-cadherin gene with susceptibility to ovarian carcinoma

Objective To investigate the association of three single nucleotide polymorphisms(SNPs),i.e.-160C/A,-347G/GA and 3′UTR+54C/T,in the promoter region of E-cadherin gene(CDHl)with the risk of epithelial ovarian carcinoma.Methods The SNPs of CDH1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)in 207 epithelial ovarian carcinoma patients and 256 unrelated healthy women;immunohistochemistry was used to measure the level of CDH1 in different genotypes of 3′UTR+54C/T locus.Results There were no significant difference in the frequencies between patients and control women in the two loci (-160C/A,-347G/GA)of CDH1 gene(P＞0.05).However,there was significant difference in the frequency of CDH1 3′-UTR+54C/T genotypes(CC,CT and TF)between patients and controls(P＜0.05).The frequencies of the CC genotype and the C allele in patients(65.2%,89.1%)were significantly higher than that in controls(52.7%,64.5%)(P＜0.01).The CC genotype significantly increased the risk to epithelial ovarian careinonla,with adjusted odds ratio of 1.85(95%CI=1.27-2.69).In the ovarian tissues of patients,the expression of CDH1 from CC genotype was significantly lower than that with the other genotypes(CT+TT)(P＜0.05).The-160C/A and-347G/GA polymorphisms were in linkage disequilibrium(D′=0.999 582)by analyzing with 2LD software.The-160A/-347GAhaplotype was only observed in patients(5.1%),the-160C/-347GA haplotype decreased susceptibility to epithelial ovarian carcinoma,with adjusted odds ratio of 0.66(95%CI=0.45-0.96).Conclusion CDH1-160C/A and -347G/GA polymorphisms were not associated with the risk of epithdial ovarian carcinoma.However,the haplotype may have impact on the risk of epithelial ovarian carcinoma.The CC genotype of 3′-UTR+54CT may be a potential risk factor for the epithelial ovarian carcinoma.