Division of Gastroenterology, Departmet of Medicine, Brigham and Women's Hospital, Harvard Medical School, and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Natl Compr Canc Netw. 2010 Jan;8(1):98-105. doi: 10.6004/jnccn.2010.0006.
Of the estimated 150,000 colorectal cancer (CRC) cases diagnosed annually, approximately 30% have a familial basis and 3% to 5% are from high-penetrance inherited cancer syndromes. Lynch syndrome, or hereditary nonpolyposis colorectal cancer, caused by inherited germline mutations in mismatch repair (MMR) genes, is the most commonly inherited CRC syndrome. It is characterized by young-onset CRC and an increased risk for extracolonic tumors, including gynecologic, urinary tract, and other gastrointestinal cancers. Commercial testing is available for mutations in the MMR genes, but testing all patients with CRC would be economically prohibitive. Therefore, a comprehensive evaluation of a multigenerational family cancer history is essential for the identification of at-risk individuals. The presence of tumors diagnosed at a young age, multiple first- and second-degree relatives with cancer, or 2 or more primary cancers may be indicative of an inherited cancer syndrome and these individuals should undergo genetic evaluation. Genetic test results, when conclusive, can guide management for patients and their families. However, indeterminate test results may provide false reassurance to patients who should be managed as being at higher-than-average risk. Online risk assessment tools and commercial genetic testing offer the potential to identify a greater number of at-risk individuals at an earlier age. However, for these measures to improve outcomes, patients must receive screening recommendations and counseling appropriate for their cancer risk.
在每年诊断出的约 15 万例结直肠癌（CRC）病例中，约 30%具有家族基础，3%至 5%来自高外显率遗传性癌症综合征。林奇综合征或遗传性非息肉病性结直肠癌，是由错配修复（MMR）基因的种系突变引起的，是最常见的遗传性 CRC 综合征。其特征是结直肠癌发病年龄较早，并且结直肠外肿瘤风险增加，包括妇科、泌尿道和其他胃肠道癌症。商业检测可用于 MMR 基因的突变，但对所有 CRC 患者进行检测在经济上是不可行的。因此，对多代家族癌症史进行全面评估对于识别高危个体至关重要。存在年轻时诊断出的肿瘤、有癌症的多个一级和二级亲属，或 2 个或更多原发性癌症，可能表明存在遗传性癌症综合征，这些个体应进行基因评估。当基因检测结果具有结论性时，可为患者及其家属的管理提供指导。然而，不确定的检测结果可能会给那些被认为风险高于平均水平的患者提供虚假的保证。在线风险评估工具和商业基因检测有可能在更早的年龄识别出更多的高危个体。然而，为了提高这些措施的效果，患者必须接受与其癌症风险相适应的筛查建议和咨询。
