Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancer. Inherited mutations in the mismatch repair genes associated with this syndrome have an approximate 80% lifetime risk of colorectal cancer. Since there are no premonitory signs of susceptibility to HNPCC, family history is the initial method for identifying those at increased risk. At risk individuals should undergo genetic counseling and testing. Although an algorithmic indication for genetic testing in at risk HNPCC patients is yet to be determined, many advocate initial screening for microsatellite instability (MSI) of the cancer specimen in individuals suspected of carrying HNPCC mutations. Those who test positive for MSI can then undergo further testing for mutations in the associated germline mismatch repair genes. Techniques for detecting these mutations currently include in vitro synthesized-protein assay, single-strand conformational polymorphism, and DNA sequencing. Given the aggressive nature of HNPCC adenomas, individuals who test positive for HNPCC mutations are recommended to undergo yearly colonoscopic surveillance starting at the age of 25. A reasonable alternative to lifetime colonoscopic surveillance for the prevention of colorectal cancer in these individuals is prophylactic colectomy. The prevention of colorectal cancer through pharmacological means is under investigation as another option in the management of HNPCC patients. Specifically, chemoprevention trials are currently ongoing to evaluate the efficacy of COX-2 inhibitors in the prevention of colorectal cancer in HNPCC and familial adenomatous polyposis patients.

中文翻译：

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遗传性非息肉性大肠直肠癌：预防管理。

遗传性非息肉性大肠癌（HNPCC）是遗传性大肠癌的最常见形式。与该综合征相关的错配修复基因中的遗传突变具有大约80％的终生结肠直肠癌风险。由于没有对HNPCC的易感迹象，因此家族史是识别高危人群的最初方法。有风险的个人应该接受遗传咨询和测试。尽管尚未确定在高危HNPCC患者中进行基因检测的算法指征，但许多人主张对怀疑携带HNPCC突变的个体进行癌症标本的微卫星不稳定性（MSI）的初步筛选。那些对MSI测试呈阳性的人可以接受进一步测试，以检查相关种系错配修复基因中的突变。目前，用于检测这些突变的技术包括体外合成蛋白测定，单链构象多态性和DNA测序。鉴于HNPCC腺瘤具有侵略性，因此建议从25岁开始对HNPCC突变测试呈阳性的患者每年进行结肠镜检查。为预防结肠直肠癌，对于这些人而言，终生结肠镜检查的合理替代方法是预防结肠直肠癌。通过药理学方法预防结直肠癌作为HNPCC患者管理的另一种选择正在研究中。具体而言，目前正在进行化学预防试验，以评估COX-2抑制剂在HNPCC和家族性腺瘤性息肉病患者中预防结肠直肠癌的功效。