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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Apr 27, 2016; 8(4): 284-293
Published online Apr 27, 2016. doi: 10.4240/wjgs.v8.i4.284
NOD2 mutations and colorectal cancer - Where do we stand?
Diogo Branquinho, Paulo Freire, Carlos Sofia
Diogo Branquinho, Paulo Freire, Carlos Sofia, Serviço de Gastrenterologia, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal
Diogo Branquinho, Paulo Freire, Carlos Sofia, Faculdade de Medicina da Universidade de Coimbra, 3004-504 Coimbra, Portugal
Author contributions: Branquinho D performed the literature search and wrote the text; Freire P and Sofia C designed the text structure and made several critical corrections and revisions until the submitted version was achieved.
Conflict-of-interest statement: The above-mentioned authors of this manuscript hereby declare that they do not have any conflict-of-interest (including but not limited to commercial, personal, political, intellectual, or religious interests) related to the work submitted herein.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Diogo Branquinho, MD, Serviço de Gastroenterologia, Centro Hospitalar e Universitário de Coimbra, Praceta Professor Mota Pinto, 3000-075 Coimbra, Portugal. diogofbranquinho@yahoo.com
Telephone: +351-914-251929 Fax: +351-239-701517
Received: July 28, 2015
Peer-review started: July 31, 2015
First decision: November 6, 2015
Revised: November 20, 2015
Accepted: February 14, 2016
Article in press: February 16, 2016
Published online: April 27, 2016
Processing time: 266 Days and 13.9 Hours
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.

Keywords: Colorectal cancer; Fecal microbiota; Cancer susceptibility; Intestinal inflammation; Nucleotide-binding and oligomerization-domain containing 2 mutations

Core tip: Recently, data from animal models showed that nucleotide-binding and oligomerization-domain containing 2 (NOD2) deficiency leads to dysbiosis and to an increased risk of colitis and colitis-associated colorectal cancer (CRC). Furthermore, it is now known that this receptor has a much more expanded role than previously thought. Concerning population-based studies, and despite initial inconsistencies, recent data points to an important role for NOD2 mutations in CRC susceptibility. Identifying carriers of such polymorphisms may allow them to be included in stricter CRC surveillance programs. A link between NOD2 mutation carriage and response to different chemotherapy regimens is also a promising field of research.