NOD2mutations and colorectal cancer - Where do we stand?

Abstract

Due to the overwhelming burden of colorectal cancer (CRC), great effort has been placed on identifying genetic mutations that contribute to disease development and progression. One of the most studied polymorphisms that could potentially increase susceptibility to CRC involves the nucleotide-binding and oligomerization-domain containing 2 (NOD2) gene. There is growing evidence that the biological activity of NOD2 is far greater than previously thought and a link with intestinal microbiota and mucosal immunity is increasingly sought after. In fact, microbial composition may be an important contributor not only to inflammatory bowel diseases (IBD) but also to CRC. Recent studies have showed that deficient NOD2 function confers a communicable risk of colitis and CRC. Despite the evidence from experimental models, population-based studies that tried to link certain NOD2 polymorphisms and an increase in CRC risk have been described as conflicting. Significant geographic discrepancies in the frequency of such polymorphisms and different interpretations of the results may have limited the conclusions of those studies. Since being first associated to IBD and CRC, our understanding of the role of this gene has come a long way, and it is tempting to postulate that it may contribute to identify individuals with susceptible genetic background that may benefit from early CRC screening programs or in predicting response to current therapeutic tools. The aim of this review is to clarify the status quo of NOD2 mutations as genetic risk factors to chronic inflammation and ultimately to CRC. The use of NOD2 as a predictor of certain phenotypic characteristics of the disease will be analyzed as well.

Identification and Characterization of Novel Receptor-Interacting Serine/Threonine‐Protein Kinase 2 Inhibitors Using Structural Similarity Analysis

“…These events subsequently drive inflammation damage indicative of what IBD patients encounter. NOD2 mutations have been observed in IBD patients, lending support for dysregulated NOD2/RIPK2 signaling driving inflammation in IBD patients (Branquinho et al, 2016). We have demonstrated the importance of Ras association domain family protein 1A [RASSF1A (or 1A)] in the pathogenesis of colitis in a rodent model (Gordon et al, 2013).…”

“…RIPK2 is the obligate kinase to the NOD2 pathogen receptor pathway and has been demonstrated to be involved in NFkB activation and metastatic behavior in some cancers (Jun et al, 2013) and has a distinct activity versus RIPK1, 3, or 4 (Chirieleison et al, 2016). In addition, several reports suggest involvement in the activation of the immune response upon viral infection (Lupfer et al, 2013) and the requirement for the NOD2/RIPK2 molecular pathway in several models on inflammatory diseases, including experimental colitis (Branquinho et al, 2016) and arthritis (Vieira et al, 2012). Colorectal cancer (CRC) is only one example of a disease that can arise from a prior state of persistent or chronic inflammation.…”

Analysis of Gene Expression in an Inbred Line of Soft-Shell Clams (Mya arenaria) Displaying Growth Heterosis: Regulation of Structural Genes and the NOD2 Pathway

“…In addition to contributing to growth, the NOD2 pathway leads to transcription of proinflammatory cytokines via TNF-alpha and NFκB [40]. The pathway has been implicated in the inflammatory bowel condition Crohn's Disease [41–43] and in cancers, particularly colorectal cancer [42, 44]. Other immune-related genes differentially expressed include a pathogenesis-related protein that was upregulated eightfold and interferon alpha-inducible protein that was downregulated 19-fold.…”

The Genetic Variations ofNOD2Are Associated With White Blood Cell Counts

“…이 외에 도 NOD2는 자가포식(Autophagy) 현상에 관여하며 NOD1 과 함께 ATG16L1을 끌어들여 자가포식 기전에 중요한 역 할을 한다 (Travassos et al, 2010). 최근에는 동물실험에서 NOD2의 결손이 대장염과 관련있는 대장직장암을 유발하 는 것으로 보고되었다 (Branquinho et al, 2016 (Cho et al, 2009 가장 높은 유전 변이임이 확인되었다 (Kong and Lee, 2012). (Hsu et al, 2008;Bergsbaken et al, 2009…”