Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and 30% of all cases of CRC are believed to have a familial component and up to one-third of these (10%) are hereditary. Pathogenic germline variants in multiple genes have been associated with predisposition to hereditary CRC or polyposis. Lynch syndrome (LS) is the most common hereditary CRC syndrome, caused by variants in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 and is inherited in a dominant manner. Heritable conditions associated with colonic polyposis include familial adenomatous polyposis (FAP) associated with APC pathogenic variants, MUTYH-associated polyposis (MAP) caused by biallelic MUTYH pathogenic variants, and polymerase proofreading–associated polyposis (PPAP) caused by POLE or POLD1 pathogenic variants. Given the overlapping phenotypes of the cancer syndromes along with the limited sensitivity of using clinical criteria alone, a multigene panel testing approach to diagnose these conditions using next-generation sequencing (NGS) is effective and efficient. This technical standard is not recommended for use in the clinic for patient evaluation. Please refer to National Comprehensive Cancer Network (NCCN) clinical practice guidelines to determine an appropriate testing strategy and guide medical screening and management. This 2021 edition of the American College of Medical Genetics and Genomics (ACMG) technical standard supersedes the 2013 edition on this topic.

结直肠癌 (CRC) 是第四大最常诊断的癌症，据信所有 CRC 病例中有 30% 具有家族成分，其中多达三分之一 (10%) 是遗传性的。多个基因中的致病性种系变异与遗传性 CRC 或息肉病的易感性有关。Lynch 综合征 (LS) 是最常见的遗传性 CRC 综合征，由错配修复 (MMR) 基因MLH1、MSH2、MSH6和PMS2的变异引起，并且以显性方式遗传。与结肠息肉病相关的遗传性疾病包括与APC致病变异相关的家族性腺瘤性息肉病 (FAP)、由双等位基因引起的MUTYH相关性息肉病 (MAP)由POLE或POLD1引起的MUTYH致病变异和聚合酶校对相关息肉病 (PPAP)致病性变异。鉴于癌症综合征的重叠表型以及单独使用临床标准的有限敏感性，使用下一代测序 (NGS) 诊断这些疾病的多基因面板测试方法是有效且高效的。本技术标准不推荐在临床上用于患者评估。请参阅国家综合癌症网络 (NCCN) 临床实践指南，以确定适当的检测策略并指导医学筛查和管理。2021 年版的美国医学遗传学和基因组学 (ACMG) 技术标准取代了关于该主题的 2013 年版。