Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease
Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease
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DOI：
10.1056/nejm199805213382101
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发表时间：
1998-05-21
影响因子：
158.5
通讯作者：
ValKamo, E
中科院分区：
文献类型：
--
作者：
Aaltonen, LA;Salovaara, R;ValKamo, E
背景使人易患结直肠癌的遗传性疾病包括息肉病综合征和遗传性非息肉病性结直肠癌。与息肉病综合征相比，遗传性非息肉病性结直肠癌缺乏独特的临床特征。然而，DNA错配修复基因的种系突变是该疾病的特征性分子特征。由于这种突变的载体的临床筛选可以帮助预防癌症，重要的是要制定适用于分子筛选这种疾病的策略。方法我们前瞻性地筛选肿瘤标本从509例连续的结直肠腺癌的DNA复制错误，这是遗传性结直肠癌的特点。这些复制错误是通过肿瘤DNA的微卫星标记分析检测到的。从复制错误患者的正常组织DNA中筛选错配修复基因MLH1和MSH2的种系突变。结果在509例患者中，63例（12%）存在复制错误。这63例患者中有10例的正常组织标本有MLH1或MSH2的种系突变。在这10名患者中（占509名患者的2%），9名患者的一级亲属患有子宫内膜癌或结直肠癌，7名患者年龄在50岁以下，4名患者既往患有结直肠癌或子宫内膜癌。结论在芬兰的这一系列结直肠癌患者中，至少2%患有遗传性非息肉病性结直肠癌。我们建议对所有符合以下一项或多项标准的结直肠癌患者进行复制错误检测：结直肠癌或子宫内膜癌家族史，年龄小于50岁，以及多发性结直肠癌或子宫内膜癌病史。发现有复制错误的患者应进行进一步的DNA错配修复基因的种系突变分析。(C)1998年，马萨诸塞州医学会。
Background Genetic disorders that predispose people to colorectal cancer include the polyposis syndromes and hereditary nonpolyposis colorectal cancer. In contrast to the polyposis syndromes, hereditary nonpolyposis colorectal cancer lacks distinctive clinical features. However, a germ-line mutation of DNA mismatch-repair genes is a characteristic molecular feature of the disease. Since clinical screening of carriers of such mutations can help prevent cancer, it is important to devise strategies applicable to molecular screening for this disease.Methods We prospectively screened tumor specimens obtained from 509 consecutive patients with colorectal adenocarcinomas for DNA replication errors, which are characteristic of hereditary colorectal cancers. These replication errors were detected through microsatellite-marker analyses of tumor DNA. DNA from normal tissue from the patients with replication errors was screened for germ-line mutations of the mismatch-repair genes MLH1 and MSH2.Results Among the 509 patients, 63 (12 percent) had replication errors. Specimens of normal tissue from 10 of these 63 patients had a germ-line mutation of MLH1 or MSH2. Of these 10 patients (2 per cent of the 509 patients), 9 had a first-degree relative with endometrial or colorectal cancer, 7 were under 50 years of age, and 4 had had colorectal or endometrial cancer previously.Conclusions In this series of patients with colorectal-cancer in Finland, at least 2 percent had hereditary nonpolyposis colorectal cancer. We recommend testing for replication errors in all patients with colorectal cancer who meet one or more of the following criteria: a family history of colorectal or endometrial cancer, an age of less than 50 years, and a history of multiple colorectal or endometrial cancers. Patients found to have replication errors should undergo further analysis for germ-line mutations in DNA mismatch-repair genes. (C) 1998, Massachusetts Medical Society.