The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer.

Chengxin Luo,Hu Zhang

doi:10.1155/2017/5126048

Abstract

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC). The risk factors of CRC in IBD patients include long disease duration, extensive colitis, severe histological inflammation, and coexistence with primary sclerosing cholangitis (PSC). Several molecular pathways that contribute to sporadic CRC are also involved in the pathogenesis of colitis-associated CRC. It is well established that long-standing chronic inflammation is a key predisposing factor of CRC in IBD. Proinflammatory pathways, including nuclear factor kappa B (NF-κB), IL-6/STAT3, cyclooxygenase-2 (COX-2)/PGE2, and IL-23/Th17, promote tumorigenesis by inducing the production of inflammatory mediators, upregulating the expression of antiapoptotic genes, and stimulating cell proliferation as well as angiogenesis. Better understanding of the underlying mechanisms may provide some promising targets for prevention and therapy. This review aims to elucidate the role of these signaling pathways in the pathogenesis of colitis-associated CRC using evidence-based approaches.

Highlights

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic incurable disease that can affect the entire gastrointestinal tract
This review aims to elucidate the role of chronic inflammation in colitis-associated colorectal cancer (CRC) with a review regarding the contribution of inflammatory signaling pathways, including nuclear factor kappa B (NF-κB), IL-6/STAT3, cyclooxygenase-2 (COX-2)/PGE2, and IL-23/Thelper IL-17-producing (Th17)
Perpetuated intestinal inflammation in IBD dramatically increases the risk of CRC

Summary

Introduction

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic incurable disease that can affect the entire gastrointestinal tract. A meta-analysis including 116 studies (54,478 patients) estimated that the overall incidence rate of CRC in patients with UC was 3/1000 py This risk increased with disease duration, which was 2% at 10 years, 8% at 20 years, and 18% at 30 years [2]. The risk increased by at least fourfold in patients with colonic disease [4] These data demonstrate that repeated inflammation is a risk factor for CRC in patients with IBD. In addition to long disease duration, extensive colitis is a risk factor for the development of CRC in IBD. This review aims to elucidate the role of chronic inflammation in colitis-associated CRC with a review regarding the contribution of inflammatory signaling pathways, including nuclear factor kappa B (NF-κB), IL-6/STAT3, cyclooxygenase-2 (COX-2)/PGE2, and IL-23/Th17

NF-κB Pathway

Findings

Conclusion