Molecular screening for hereditary nonpolyposis colorectal cancer:: A prospective, population-based study
Molecular screening for hereditary nonpolyposis colorectal cancer:: A prospective, population-based study
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DOI：
10.1200/jco.2001.19.19.3944
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发表时间：
2001-10-01
影响因子：
45.3
通讯作者：
de Leon, MP
中科院分区：
文献类型：
--
作者：
Percesepe, A;Borghi, F;de Leon, MP
目的：错配修复基因的种系突变是遗传性非息肉病性结直肠癌的易感基因。为了解决有效的筛查计划，必须知道这种疾病的真实发病率。以前的临床研究报告了大约0.5%到13%的结直肠癌(CRC)病例，而芬兰的生物分子研究发现，这种疾病的突变携带者的发病率为2%到2.7%。本报告的目的是建立结肠癌高发区的发病率。患者和方法：通过当地结直肠癌登记的数据，我们前瞻性地收集了1996年1月1日至1997年12月31日的所有结直肠癌病例(N=391例)。用6~12个单核苷酸和双核苷酸标记对336例结直肠癌进行了微卫星不稳定性筛查，占发病病例的85.9%。对MSI病例进行MSH2和MLH1胚系突变分析及免疫组织化学检测，检测MLH1启动子区域甲基化情况。MSI病例与微卫星稳定(MSS)病例在近端位置(P<；.01)、高粘液成分(P<；.01)和低分化(P<；.01)方面有显著差异(P=0.002)。在所研究的MSI病例(n=12)中，只有一例具有与HNPCC相容的家族史的胚系突变(MSH2)。另外5名有HNPCC家族病史的患者(2名MSI和3名MSS肿瘤)没有显示出胚系突变。结论：我们得出结论：在结直肠癌高发区，分子确认的HNPCC的发生率(1[0.3%])低于先前的生物分子和临床估计。(C)2001年，由美国临床肿瘤学会主办。
Purpose : Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer.Patients and Methods: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleoticle markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1.Results: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P < .01), high mucinous component (P < .01), and poor differentiation (P = .002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations.Conclusion: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates. (C) 2001 by American Society of Clinical Oncology.