Strate Lisa L, Syngal Sapna
Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA 02115, USA.
Cancer Causes Control. 2005 Apr;16(3):201-13. doi: 10.1007/s10552-004-3488-4.
The purpose of this article is to review the genetic colorectal cancer syndromes including Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Family Polyposis (FAP) and the hamartomatous polyposis syndromes. HNPCC is the most common of the hereditary colorectal cancer syndromes, and is the result of defects in the mismatch repair genes. Individuals with HNPCC have an 80 lifetime risk of colorectal cancer, and in females a 30-50% risk of endometrial cancer, as well as predisposition for a number of other malignancies. Early screening and interval surveillance for colorectal and endometrial cancer are recommended. In FAP, mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene give rise to hundreds to thousands of colorectal polyps, some of which will inevitably progress to cancer. Early diagnosis and timely prophylactic colectomy prevent this outcome. Chemoprevention with nonsteroidal anti-inflammatory drugs can reduce adenoma number and size in FAP, but the effect is incomplete. In addtion, surveillance for upper gastrointestinal tract malignancies is necessary. Attenuated forms of FAP may be the result of mutations in the APC gene, or in the recently described MYH gene. Mutations in the MYH gene should be considered in individuals with multiple adenomas whose family history does not reflect an autosomal dominant pattern of inheritance. The hamartomatous polyposis syndromes are uncommon but distinctive disorders in which multiple hamartomatous polyps develop at a young age. Our understanding of the genetic basis of these disorders is improving, and a predisposition for gastrointestinal and other malignancies has recently been recognized. This article summarizes the genetics, clinical manifestations and clinical management of each of these syndromes with an emphasis on genetic testing and prevention.
本文旨在综述遗传性结直肠癌综合征，包括遗传性非息肉病性结直肠癌（HNPCC）、家族性腺瘤性息肉病（FAP）和错构瘤性息肉病综合征。HNPCC是最常见的遗传性结直肠癌综合征，是错配修复基因缺陷的结果。患有HNPCC的个体患结直肠癌的终生风险为80%，女性患子宫内膜癌的风险为30%-50%，此外还易患多种其他恶性肿瘤。建议对结直肠癌和子宫内膜癌进行早期筛查和定期监测。在FAP中，腺瘤性息肉病 coli（APC）肿瘤抑制基因突变会导致数百至数千个结直肠息肉，其中一些不可避免地会发展为癌症。早期诊断和及时的预防性结肠切除术可避免这种情况。使用非甾体抗炎药进行化学预防可减少FAP中的腺瘤数量和大小，但效果不完全。此外，对上消化道恶性肿瘤进行监测是必要的。FAP的弱化形式可能是APC基因或最近描述的MYH基因突变的结果。对于有多个腺瘤但其家族史不反映常染色体显性遗传模式的个体，应考虑MYH基因突变。错构瘤性息肉病综合征并不常见，但却是一种独特的疾病，其中多个错构瘤性息肉在年轻时出现。我们对这些疾病的遗传基础的理解正在提高，最近已经认识到它们易患胃肠道和其他恶性肿瘤。本文总结了每种综合征的遗传学、临床表现和临床管理，重点是基因检测和预防。
