Inflammation in Colorectal Cancer Inflammatory Bowel Disease, and Diabetes Mellitus: The Link

Abstract

IntroductionVarious chronic diseases like Inflammatory bowel disease (IBD), colorectal cancer (CRC) and Type 2 diabetes mellitus (T2DM) are triggered by infection and or unregulated chronic inflammation. Where is the link?InflammationInflammation is basically a beneficial complex response which may involve a panel of bioactive pro‐and anti‐inflammatory molecules. However, a persistent or an inadequately resolved chronic inflammation may increase the risk of several pathologies such as IBD, CRC and T2DM, through toxic factors and bioactive molecules promoting epithelial‐mesenchymal transition (EMT) and facilitating carcinogenesis through the activation of JAK/STAT signaling pathway (IL‐6, TNF‐α), the differential phosphorylation of SMAD's which induce EMT (TGFB's), or mechanisms involving reduced oxygen species (ROS) and reactive nitrogen species (RNS).CRC and IBD: It is widely accepted that IBD patients have a higher risk of CRC. The IBD's are multifactorial pathologies involving alterations in the microbiota which can induce chronic inflammation leading to a potential role in carcinogenesis through mediators relevant in EMT induction like TGFB, TNF‐α , IL‐6, ROS and others.T2DM: Multiple inflammatory mechanisms provoke the pathogenesis of T2DM through mediators like (TNF‐α, IL‐6, IL‐8, and TGFB, which may alter the normal structure of the β‐cells by inducing pancreatic islet's apoptosis, thus the leading to the release of insulin‐like growth factor ‐1 (IGF‐1) which stimulates EMT, and carcinogenesis. In T2DM, Hyperglycemia contributes to the onset of inflammation, the increase of ROS, and triggering of inflammatory cytokines while hyperinsulinemia activates IGF‐1 over production which induces EMT and activates two mitogenic pathways that favor cancer growth: P13K/AKK and β‐catenin pathwaysConclusionIBD, CRC and T2DM are commonly interrelated clinical problems. They share a common basis influenced by disease‐related inflammation enhanced by changes in the endocrine milieu.