CAJ | 학술논문

目的分析和比较汉族和朝鲜族遗传性非息肉性结直肠癌(hereditary nonpolyposis colorectal cancer,HNPCC)家系的临床及遗传学表型的异同点.方法收集31个中国的汉族家系和63个韩国的朝鲜族家系先证者和家系成员的各项临床资料,对先证者外周血DNA进行相关基因hMLH和hMSH2的种系突变检测.应用聚合酶链反应-单链构象多态性分析或变性高效液相色谱法筛查突变,对结果异常的样本进行DNA测序.结果 31个汉族家系中共发生136例次恶性肿瘤,其中结直肠癌106例次,占所有肿瘤患者的77.9%,诊断年龄平均为(48.6±29.0)岁;其次为胃癌共14例.经突变检测,31例汉族先证者中有7例被检出含有hMLH1(3个)或hMSH2(4个)基因的病理性突变,总突变率为22.6%.其中错义突变2个、无义突变2个、移码突变2个、大片段缺失1个.63个朝鲜族家系中共发生293例次恶性肿瘤,其巾结直肠癌242例次,占所有肿瘤患者的82.6%,诊断年龄平均为(45.9±11.0)岁;胃癌同样也是第2大常见肿瘤类型,共发生21例.63例朝鲜族先证者中有19例被检测出含有hMLH1(17个)或hMSH2(2个)基因的突变,总突变率为30.2%.其中12个为移码突变,5个为错义突变,1个为无义突变,1个为剪接位点的碱基改变导致异常剪接.结论 (1)汉族与朝鲜族HNPCC家系在临床表现上相似,均有发病年龄轻、以远端结肠癌和直肠癌多见、多原发大肠癌发生率较两方国家低、肠外肿瘤以胃癌最多见等特点.(2)遗传表型方面,汉族与朝鲜族HNPCC家系的总突变率相似,但均低于西方国家的报道.两个种族的家系中的突变基因、突变类型和突变分布上存在差异及各自的特征.
목적 분석화비교한족화조선족유전성비식육성결직장암(hereditary nonpolyposis colorectal cancer,HNPCC)가계적림상급유전학표형적이동점.방법 수집31개중국적한족가계화63개한국적조선족가계선증자화가계성원적각항림상자료,대선증자외주혈DNA진행상관기인hMLH화hMSH2적충계돌변검측.응용취합매련반응-단련구상다태성분석혹변성고효액상색보법사사돌변,대결과이상적양본진행DNA측서.결과 31개한족가계중공발생136례차악성종류,기중결직장암106례차,점소유종류환자적77.9%,진단년령평균위(48.6±29.0)세;기차위위암공14례.경돌변검측,31례한족선증자중유7례피검출함유hMLH1(3개)혹hMSH2(4개)기인적병이성돌변,총돌변솔위22.6%.기중착의돌변2개、무의돌변2개、이마돌변2개、대편단결실1개.63개조선족가계중공발생293례차악성종류,기건결직장암242례차,점소유종류환자적82.6%,진단년령평균위(45.9±11.0)세;위암동양야시제2대상견종류류형,공발생21례.63례조선족선증자중유19례피검측출함유hMLH1(17개)혹hMSH2(2개)기인적돌변,총돌변솔위30.2%.기중12개위이마돌변,5개위착의돌변,1개위무의돌변,1개위전접위점적감기개변도치이상전접.결론 (1)한족여조선족HNPCC가계재림상표현상상사,균유발병년령경、이원단결장암화직장암다견、다원발대장암발생솔교량방국가저、장외종류이위암최다견등특점.(2)유전표형방면,한족여조선족HNPCC가계적총돌변솔상사,단균저우서방국가적보도.량개충족적가계중적돌변기인、돌변류형화돌변분포상존재차이급각자적특정.
Objective To compare thc clinical and genetic features between Chinese and Korean hereditary nonpolyposis coloreetal cancer(HNPCC)families.Methods Thirty-one Chinese HNPCC families and 63 HNPCC Korean families were involved in this study.The cunical data of the probands and families were coilected.Genomic DNAs were prepared from peripheral blood samples of probands for DNA test.PCR and DHPLC were employed to screen the mutations. Sequencing analysis was followed to find out the exact mutation site and feature in samples showing abnormalities in SSCP or DHPLC analysis.Results In a total. There were 136 malignant neoplasms diagnosed in the 31 Chinese fami1ies,about 77.9% of them were colorectal cancer. The mean age of colorectal cancer at diagnosis was(48.6 4 ±29.0) years.Gastric cancer was the second most common cancer in these families. Seven pathogenic mutations(3 in hMLH1 gene and 4 in hMSH2 gene) were detected in the 31 probands,including 2 missense mutations,2 nollsense mutations.2 frameshift mutations and 1 large-fragment deletion.The total mutation rate Ws3 22.6%.In the 63 Korean families.293 maligrkant neoplasms were documented,82.6%of them were diagnosed as colorectal cancer.The mean age of colorectal cancer at diagnosis Was(45.9±11.0)years.Gastric cancer was also the most common extracolonic cancer in these Kolean families.Nineteen pathogenic mutations(17 in hMLH1 gene and 2 in hMSH2 genes) were detected in the 63 pmbands, including 12 frameshift mutations, 5 missense mutations,1 nonsense mutation and 1 base-chenge at the sDlicing site. The total mutation rate was 30.2%.Condsulon (1) Chinese and Korean HNPCC families had many similar clinical features, such as early-onset of colorectal cancer. Predominance in distal colon and rectum, lower incidence of synchronous or metachronous colorectal cancels as compared with Westem countries,and a frequent occurrence of gastric cancer in the families.(2)The total mutation rate of hNIH1 and hMSH2 gene in Chinese and Korean HNPCC families was similar and lower than that reported in Westem countries.But the mutation characteristics, Such as predominant gene,mutation type and mutation distilbution,were different in the two populations.