The present article summarizes recent developments in the characterization of genetic predisposition to colorectal cancer (CRC). The main themes covered include new hereditary CRC and polyposis syndromes, non-CRC hereditary cancer genes found mutated in CRC patients, strategies used to identify novel causal genes, and review of candidate genes that have been proposed to predispose to CRC and/or colonic polyposis. We provide an overview of newly described genes and syndromes associated with predisposition to CRC and polyposis, including: polymerase proofreading-associated polyposis, NTHL1-associated polyposis, mismatch repair gene biallelic inactivation-related adenomatous polyposis (including MSH3- and MLH3-associated polyposes), GREM1-associated mixed polyposis, RNF43-associated serrated polyposis, and RPS20 mutations as a rare cause of hereditary nonpolyposis CRC. The implementation of next generation sequencing approaches for genetic testing has exposed the presence of pathogenic germline variants in genes associated with hereditary cancer syndromes not traditionally linked to CRC, which may have an impact on genetic testing, counseling and surveillance. The identification of new hereditary CRC and polyposis genes has not deemed an easy endeavor, even though known CRC-related genes explain a small proportion of the estimated familial risk. Whole-genome sequencing may offer a technology for increasing this proportion, particularly if applied on pedigree data allowing linkage type of analysis. The final section critically surveys the large number of candidate genes that have been recently proposed for CRC predisposition.

本文总结了大肠癌遗传易感性表征的最新进展。涵盖的主题包括新的遗传性CRC和息肉病综合征，在CRC患者中发现突变的非CRC遗传性癌症基因，用于鉴定新的致病基因的策略以及审查已提议易患CRC和/或结肠息肉的候选基因。我们提供了与CRC和息肉病易感性相关的新描述基因和综合征的概述，包括：聚合酶校对相关息肉病，NTHL1相关息肉病，错配修复基因双等位基因失活相关腺瘤性息肉病（包括MSH3和MLH3相关息肉）。 ，GREM1相关的混合性息肉病，RNF43相关的锯齿状息肉病和RPS20突变是遗传性非息肉性CRC的罕见原因。下一代用于基因检测的测序方法的实施暴露了与遗传性癌症综合症相关的基因中病原种系变异的存在，而这些基因在传统上并不与CRC相关联，这可能会对基因检测，咨询和监测产生影响。尽管已知的与CRC相关的基因解释了估计的家族性风险的一小部分，但鉴定新的遗传性CRC和息肉病基因并不容易。全基因组测序可能会提供一种增加该比例的技术，尤其是将其应用于允许链接类型分析的谱系数据时。最后一部分对最近提出的用于CRC易感性的大量候选基因进行了严格的调查。