From Chronic Inflammation to Colitis-Associated Colorectal Cancer: Field Cancerization and Clonal Evolution
- 1Department of Gastroenterological Surgery, The University of Osaka, Osaka 565-0871, Japan
- 2Department of Colorectal Surgery, Dokkyo Medical University, Tochigi 321-0293, Japan
Abstract
Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer, particularly in patients with long-standing and extensive disease. Although advances in medical therapy and surveillance have reduced colorectal cancer incidence, prolonged preservation of chronically inflamed colonic mucosa has increased the importance of understanding how cumulative inflammation promotes carcinogenesis. UC-associated neoplasia differs from sporadic colorectal cancer in its multifocality, pathological heterogeneity, and molecular evolution. Repeated inflammation, epithelial injury, and regeneration promote the accumulation of somatic and epigenetic alterations across histologically non-dysplastic mucosa, generating a cancerized field composed of genetically heterogeneous epithelial clones. Recent sequencing studies have shown that many clones selected in chronically inflamed mucosa harbor alterations that enhance adaptation to inflammatory stress but are not necessarily premalignant, indicating that field cancerization represents a dynamic evolutionary ecosystem rather than simple expansion of cancer-prone clones. Neoplastic progression requires further clonal selection as the selective environment shifts toward autonomous growth. Colitis-associated colorectal cancer is characterized by early TP53 alterations, a relatively late and less frequent involvement of APC, branching clonal evolution, and substantial copy-number alterations, particularly during progression from low- to high-grade dysplasia. Thus, colitis-associated carcinogenesis can be understood as a process in which chronic inflammation establishes a genetically altered field, followed by dynamic clonal selection and genomic evolution. Elucidating these processes may enable identification of high-risk fields and clones before invasive cancer develops and provide a biological basis for improved surveillance, risk stratification, and chemoprevention.
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BibTeX
@article{ogino2026from,
title = {{From Chronic Inflammation to Colitis-Associated Colorectal Cancer: Field Cancerization and Clonal Evolution}},
author = {Takayuki Ogino and Yuki Sekido and Tsunekazu Mizushima and Ryota Mori and Mitsunobu Takeda and Masaaki Miyo and Atsushi Hamabe and Norikatsu Miyoshi and Mamoru Uemura and Hidetoshi Eguchi},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203247},
url = {https://www.mdpi.com/2072-6694/18/20/3247},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From Chronic Inflammation to Colitis-Associated Colorectal Cancer: Field Cancerization and Clonal Evolution
AU - Takayuki Ogino
AU - Yuki Sekido
AU - Tsunekazu Mizushima
AU - Ryota Mori
AU - Mitsunobu Takeda
AU - Masaaki Miyo
AU - Atsushi Hamabe
AU - Norikatsu Miyoshi
AU - Mamoru Uemura
AU - Hidetoshi Eguchi
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203247
UR - https://www.mdpi.com/2072-6694/18/20/3247
AB - Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer, particularly in patients with long-standing and extensive disease. Although advances in medical therapy and surveillance have reduced colorectal cancer incidence, prolonged preservation of chronically inflamed colonic mucosa has increased the importance of understanding how cumulative inflammation promotes carcinogenesis. UC-associated neoplasia differs from sporadic colorectal cancer in its multifocality, pathological heterogeneity, and molecular evolution. Repeated inflammation, epithelial injury, and regeneration promote the accumulation of somatic and epigenetic alterations across histologically non-dysplastic mucosa, generating a cancerized field composed of genetically heterogeneous epithelial clones. Recent sequencing studies have shown that many clones selected in chronically inflamed mucosa harbor alterations that enhance adaptation to inflammatory stress but are not necessarily premalignant, indicating that field cancerization represents a dynamic evolutionary ecosystem rather than simple expansion of cancer-prone clones. Neoplastic progression requires further clonal selection as the selective environment shifts toward autonomous growth. Colitis-associated colorectal cancer is characterized by early TP53 alterations, a relatively late and less frequent involvement of APC, branching clonal evolution, and substantial copy-number alterations, particularly during progression from low- to high-grade dysplasia. Thus, colitis-associated carcinogenesis can be understood as a process in which chronic inflammation establishes a genetically altered field, followed by dynamic clonal selection and genomic evolution. Elucidating these processes may enable identification of high-risk fields and clones before invasive cancer develops and provide a biological basis for improved surveillance, risk stratification, and chemoprevention.
SN - 2072-6694
ER -