Sustained chronic inflammation of the large intestine leads to tissue damage and repair, which is associated with an increased incidence of colitis-associated colorectal cancer (CAC). The genetic makeup of CAC is somewhat similar to sporadic colorectal carcinoma (sCRC), but there are differences in the sequence and timing of alterations in the carcinogenesis process. Several models have been developed to explain the development of CAC, particularly the “field cancerization” model, which proposes that chronic inflammation accelerates mutagenesis and selects for the clonal expansion of phenotypically normal, pro-tumorigenic cells. In contrast, the “Big Bang” model posits that tumorigenic clones with multiple driver gene mutations emerge spontaneously. The details of CAC tumorigenesis—and how they differ from sCRC—are not yet fully understood. In this Review, we discuss recent genetic, epigenetic, and environmental findings related to CAC pathogenesis in the past five years, with a focus on unbiased, high-resolution genetic profiling of non-dysplastic field cancerization in the context of inflammatory bowel disease (IBD).

大肠的持续慢性炎症会导致组织损伤和修复，这与结肠炎相关结直肠癌（CAC）的发病率增加有关。CAC 的基因组成与散发性结直肠癌 (sCRC) 有点相似，但致癌过程中改变的顺序和时间存在差异。已经开发了几种模型来解释 CAC 的发展，特别是“现场癌化”模型，该模型提出慢性炎症加速诱变并选择表型正常的促肿瘤细胞的克隆扩增。相比之下，“大爆炸”模型认为，具有多个驱动基因突变的致瘤克隆会自发出现。CAC 肿瘤发生的细节以及它们与 sCRC 有何不同尚未完全了解。在这篇综述中，我们讨论了过去五年中与 CAC 发病机制相关的最新遗传、表观遗传和环境发现，重点是炎症性肠病 (IBD) 背景下非发育不良区域癌化的公正、高分辨率遗传分析。 ）。