CAJ | 학술논문

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.
목적 탐토E-개점단백기인(E-cadherin gene,CDH1)단핵감산다태성(single nucleotide polymorphism,SN-P)여상피성란소암발병풍험적관계.방법 채용취합매련반응-한제성편단장도다태성방법분석207례상피성란소암환자화256명건강대조적CDH1기인계동자구-160C/A、-347G/GA화3′UTR+54C/T3개SNP위점기인형빈솔분포;채용면역조직화학방법검측휴대3′UTR+54C/T SNP위점불동기인형적란소암환자암조직CDH1기인적표체정황.결과 CDH1기인-160C/A화-347G/GA 2개SNP위점적기인형화등위기인빈솔분포재환자조여건강대조조간차이무통계학의의(P＞0.05).3′UTR+54C/T SNP 위점적기인형여등위기인빈솔분포재환자여건강대조조간차이유통계학의의,환자조중CC기인형화C등위기인빈솔(65.2%,89.1%)명현고우대조조(52.7%,64.5%)(P＜0.01);CC기인형가능현저증가상피성란소암적발병풍험(비치비위1.85,95%가신구간위1.27～2.69);차면역조화연구표명CC기인형환자암조직CDH1기인적표체명현저우T등위기인(CT+TT)휴대자(P＜0.05).채용2LD연건분석현시-160C/A、-347G/GA량위점간존재련쇄불평형(D′=0.999 582),-160A/-347GA단배형부재환자조중검측도(5.1%),-160C/-347GA단배형가능명현강저란소암적발병풍험(비치비위0.66,95%가신구간위0.45～0.96).결론 CDH1기인-160C/A、-347G/GA SNP가능여상피성란소암적발병풍험무관,단량위점적단배형가능개변상피성란소암적발병풍험.3′UTR+54C/T다태CC기인형가능성위상피성란소암발병적잠재위험인소.
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.