Colorectal carcinoma in the course of inflammatory bowel diseases

Abstract

Background Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are the most prevalent diseases of the digestive system, and their association is unequivocal. A long-standing inflammatory process is one of the causes of sporadic as well as inherited cancers as it impacts on malignant transformation in a wide variety of neoplastic diseases, including colorectal cancer. Methods An extensive publication search was performed in Medline and PubMed database. The keywords: colorectal carcinoma, inflammation, Crohn disease, ulcerative colitis and inflammatory bowel disease were used. Results The nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll like receptor (TLR) signaling pathways are clearly involved in the inflammatory process and are therefore implicated in the transformation of normal colonic mucosa to premalignant and malignant disease. Focal sites of inflammation could significantly increase the risk of initiation and development of cancer. Altered inflammatory activity is likely to be a result of either a disturbance of intestinal bacterial flora or an inadequate cellular response to it. Additionally, increasing the level of inflammation-related factors may also interfere with the control of cellular proliferation. Conclusions This review shows an overview of the genetic and environmental factors that appear to influence both the occurrence of IBD and CRC with particular reference to NOD2 and TLRs as well as pro- and anti-inflammatory cytokines associated with tumor initiation and progression (encompassing both tumor invasion and metastases), as they constitute potential targets for therapeutic intervention.

DNA Damage Response and Immune Defense

“…Usually, chronic inflammation is followed by the generation of ROS/RNS that, in turn, provoke oxidative DNA damage and the impairment of DNA repair pathways, thus promoting cell transformation. For instance, patients with Crohn’s disease (CD) and chronic intestinal inflammation were reported to accumulate high levels of ROS/RSN in colonic mucosa, correlated with disease severity and colorectal cancer [ 143 , 144 ]. In asbestosis, inflammatory condition triggered by the exposure to asbestos, neutrophils and macrophages release ROS, increasing the level of oxidative DNA damage and causing malignant mesothelioma (MM) in tumor arising from mesothelial cells [ 93 , 94 , 95 , 145 ].…”

Fusobacterium nucleatum Accelerates the Progression of Colitis-Associated Colorectal Cancer by Promoting EMT

“…Chronic inflammation has been found to play a key role in the progression of colon cancers. Numerous studies have shown that inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis (UC), are associated with the development and progression of CRC [ 4 , 5 , 6 ]. It has been reported that 25% of patients with IBD have colon cancer [ 7 , 8 ].…”

Influence of Iron on the Gut Microbiota in Colorectal Cancer

“…Patients with inflammatory bowel disease are at a higher risk of developing colorectal cancer compared to the general population. Similar to colorectal cancer, the pathology of inflammatory bowel disease involves alterations in the microbiota and is also associated with anemia, with patients requiring iron therapy [132,133]. Human clinical studies investigating oral iron against intravenous iron therapy on the intestinal microbiota in patients with inflammatory bowel disease have been conducted by Lee et al They found that oral iron differentially altered both bacterial phylotypes and fecal metabolites compared to intravenous iron therapy notably leading to a decreased Faecalibacterium prausnitzii and Ruminococcus bromi abundance following oral iron therapy [122].…”

“…A decreased abundance of these bacteria in inflammatory bowel disease patients can, therefore, contribute to the pathogenesis of disease through contributing to inflammation [137]. As inflammatory bowel disease can be a premalignant condition, the microbial mechanisms underpinning the pathology of the condition may have a similarity to those in colorectal cancer [132]. Hence, the negative impact of oral iron therapy on the microbiota in inflammatory bowel disease may act as an indicator of the potential outcomes in colorectal cancer.…”