Molecular mechanisms in colitis-associated colorectal cancer

Abstract

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).

Mitotic Spindle Positioning (MISP) Facilitates Colorectal Cancer Progression by Forming a Complex with Opa Interacting Protein 5 (OIP5) and Activating the JAK2-STAT3 Signaling Pathway

“…Colorectal cancer (CRC) is the third leading cause of tumor-related deaths worldwide [ 1 ]. The majority of human CRC cases are not caused by hereditary genetic changes but rather by environmental risk factors such as chronic inflammation, food-associated mutagens, and specific intestinal microbiota [ 2 ]. Among these environmental risk factors, chronic inflammation is the most significant risk factor for CRC carcinogenesis.…”

Current understandings of colibactin regulation

“…It is well established that there are both environmental (diet, lifestyle) and genetic factors which influence the risk of developing CRC [ 3 ]. Individuals with inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn’s disease are at an increased risk of developing CRC, known as colitis-associated colorectal cancer (CA-CRC) [ 4 ]. Low-fibre, ultra-processed Westernised diets are known to be linked with increased CRC risk, and the adoption of this diet is likely a factor in the increasing CRC cases being seen in some demographics [ 1 ].…”