Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
J Gastroenterol Hepatol. 2012 Sep;27(9):1423-31. doi: 10.1111/j.1440-1746.2012.07200.x.
Colorectal cancer (CRC) is the second most common newly diagnosed cancer and accounts for the second highest number of cancer related deaths in Australia, the third worldwide and of increasing importance in Asia. It arises through cumulative effects of inherited genetic predispositions and environmental factors. Genomic instability is an integral part in the transformation of normal colonic or rectal mucosa into carcinoma. Three molecular pathways have been identified: these are the chromosomal instability (CIN), the microsatellite instability (MSI), and the CpG Island Methylator Phenotype (CIMP) pathways. These pathways are not mutually exclusive, with some tumors exhibiting features of multiple pathways. Germline mutations are responsible for hereditary CRC syndromes (accounting for less than 5% of all CRC) while a stepwise accumulation of genetic and epigenetic alterations results in sporadic CRC. This review aims to discuss the genetic basis of hereditary CRC and the different pathways involved in the process of colorectal carcinogenesis.
结直肠癌（CRC）是澳大利亚第二常见的新诊断癌症，也是癌症相关死亡人数第二多的癌症，在全球范围内排名第三，在亚洲的重要性日益增加。它是通过遗传易感性和环境因素的累积效应产生的。基因组不稳定性是将正常结肠或直肠黏膜转化为癌的一个组成部分。已经确定了三种分子途径：染色体不稳定性（CIN）、微卫星不稳定性（MSI）和 CpG 岛甲基化表型（CIMP）途径。这些途径并非相互排斥，有些肿瘤表现出多种途径的特征。种系突变导致遗传性 CRC 综合征（占所有 CRC 的不到 5%），而遗传和表观遗传改变的逐步积累导致散发性 CRC。本综述旨在讨论遗传性 CRC 的遗传基础以及结直肠癌变过程中涉及的不同途径。
