中国人HNPCC家系的临床特征及M3胆碱能受体基因(A)_8区突变检测  

Clinical features and mutation analysis of a poly-(A)_8 tract in M3 cholinergic receptor gene in Chinese HNPCC families

作　　者：曹文明[1] 袁瑛[1] 宋永茂[1] 蔡善荣[1] 张苏展[1] 

机构地区：[1]浙江大学医学院附属第二医院,浙江杭州310009

出　　处：《浙江大学学报（医学版）》2004年第5期399-402,共4页Journal of Zhejiang University(Medical Sciences)

基　　金：国家高技术研究发展计划 ( 86 3计划 )基金( 2 0 0 1AA2 2 7111)

摘　　要：目的 :分析中国人遗传性非息肉病性大肠癌 (HNPCC)家系的临床特征并检测这些家系中 M3胆碱能受体基因 (A) 8区的突变情况。方法 :根据 2 0 0 3年 4月杭州会议制定的中国人 HNPCC家系标准收集 HNPCC家系共15个 ,分析其临床特征 ;提取先证者的外周血基因组 DNA,PCR扩增 M3胆碱能受体基因第 8外显子中一段长 15 3bp,包含有微卫星位点 (A) 8的基因片段 ,直接进行 DNA测序。结果 :15个家系共有恶性肿瘤患者 5 5例 ,其中大肠癌患者 4 1例 ,平均每个家系发生大肠癌 2 .73例 ,73%的大肠癌患者发病年龄 <5 0岁 ,5 1%的病灶位于近端结肠 ,4 0 %发生在直肠肛门 ,同时和异时多原发大肠癌总发生率为 12 % ,2 /3的家系属于 Lynch 型 ,共发生肠外恶性肿瘤 14例 (18个 ) ,其中胃癌最常见。 15例先证者外周血中无 1例检测到 M3胆碱能受体基因 (A) 8区的突变。结论 :M3胆碱能受体基因与中国人群中 HPNCC的发病可能无密切关系。中国人 HNPCC家系标准应在临床工作中推广应用 。Objective: To characterize the clinical features of Chinese HNPCC families and to screen the mutations of a poly (A) 8 tract in M3 cholinergic receptor gene in these families. Methods: The clinical features of 15 Chinese HNPCC families were characterized. Genomic DNAs from 15 probands were prepared. PCR and direct DNA sequencing analysis were employed to examine the mutations of a poly (A) 8 tract in exon 8 of M3 cholinergic receptor gene. Results: Total 55 cancer patients were found in 15 families including 41 cases of colorectal carcinoma with an average of 2.73 colorectal carcinomas developed per family. Thirty out of forty one (73%) patients were diagnosed before age of 50 years. Proximal colon was involved in 51% of patients, while anus and rectum were 40%. Synchronous and metachronous multiple colorectal cancers developed in 5 patients (12%). Two thirds of families belonged to Lynch Ⅱ syndrome, and total 18 extracolonic malignancies in 14 patients were identified. Gastric carcinoma was the most common extrocolonic types. In 15 HNPCC probands, no mutation was detected in the poly (A) 8 tract of exon 8 of M3 cholinergic receptor gene. Conclusion: M3 cholinergic receptor gene might have little relation with HNPCC in Chinese population. The criteria for Chinese HNPCC are useful and practical in clinical application.

关 键 词：结直肠肿瘤 遗传性非息肉性 M3胆碱能受体 基因表达 突变 

分 类 号：R735.3[医药卫生—肿瘤]