ABSTRACT
Chronic inflammatory diseases, depending upon the duration and severity, are frequently associated with an increased risk of developing cancer. A classic paradigm is the enhanced risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). Carcinogenesis is a multifactorial process that involves accumulation of genetic defects, protein modification, and cell-matrix interaction. In this review, we discuss aspects of chronic inflammation in IBD that influence the development of CRC and highlight the key molecular mediators involved in this process. Also, we identify potential targets that could facilitate earlier detection of dysplasia. The targeted manipulation of specific molecules or pathways could provide opportunities for the development of therapeutic and chemopreventive interventions, which may prove effective in arresting the progression of colitis-associated cancer (CAC), with clinical implications.
Subject(s)
Colorectal Neoplasms/etiology , Inflammatory Bowel Diseases/complications , Colitis/complications , Colorectal Neoplasms/genetics , Colorectal Neoplasms/prevention & control , Extracellular Matrix/metabolism , Gastrointestinal Tract/microbiology , Humans , Inflammation Mediators/metabolism , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/therapy , Intercellular Signaling Peptides and Proteins/metabolism , Matrix Metalloproteinases/metabolism , Metagenome , Probiotics/therapeutic use , Receptors, Cell Surface/metabolismABSTRACT
When patients with inflammatory bowel disease (IBD) are admitted to the hospital with a flare of acute severe colitis, the possibility of a concurrent cytomegalovirus (CMV) infection causing or worsening the colitis is often considered. IBD patients are usually immunosuppressed, and therefore presumably at increased risk for active CMV infection and disease. Multiple techniques are used to diagnose CMV infection, including endoscopy, histology, serology, viral culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC) performed on colon biopsy specimens with monoclonal antibodies directed against CMV immediate early antigen is considered by most to be the current gold standard for diagnosis. The prevalence of CMV infection in acute severe colitis appears to be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup of these patients is 33-36%. After antiviral therapy, colitis remission rates in IBD patients with CMV infection range from 67% to 100%, though CMV histological infection or the presence of circulating virus alone is not always associated with steroid resistance, and may not require antiviral therapy.
