Gut and Liver 2017; 11(5): 733-734 https://doi.org/10.5009/gnl16389 Active Helicobacter pylori Infection Is a Risk Factor for Colorectal Mucosa: Early and Advanced Colonic Neoplasm Sequence
Author Information
Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Panagiotis Katsinelos, Emmanuel Gavalas, Dimitri Tzivras, Christos Zeglinas, Constantinos Kountouras, Elizabeth Vardaka, Eyripidis Stefanidis, and Evagelos Kazakos
Department of Gastroenterology, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

Jannis Kountouras, Department of Gastroenterology, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, Thessaloniki 551 33, Greece, Tel: +30-2310-892238, Fax: +30-2310-992794, E-mail: jannis@auth.gr
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Body

To the Editor:

Based on serology, Lee et al.1 concluded that Helicobacter pylori infection (Hp-I) increased the risk of advanced colorectal neoplasm (CRN), particularly when combined with atrophic gastritis (AG), thereby warranting strict colonoscopy screening and surveillance in Hp-positive AG patients. Indeed, Hp-related chronic gastritis could be involved in an increased risk of CRN that seems to be enhanced by the progression of gastric atrophy and the occurrence of active inflammation.2

However, the serological test does not accurately discriminate between current and past infections, also mentioned by the aurhors,1 and, apart from past infection that might even be more relevant for oncogenesis, such a distinction is crucial because only current Hp-I induces humoral and cellular immune responses that induce or perpetuate chronic inflammatory processes in gastrointestinal tract with potential oncogenic sequelae; many neoplasms including colorectal carcinoma (CRC) arise at the sites of chronic inflammation and infection.3,4

Based on histology, the practical gold standard for current Hp-I diagnosis, our data in 50 CRC patients, 25 patients with colorectal adenomas (CRA) and 10 controls, showed significantly higher presence of Hp-I in the CRA (68%) and CRC (84%) groups compared with controls (30%).5 Regarding the features of histological severity in CRA group, presence of Hp-I was observed in 50% of patients with mild and 80% of patients with moderate/severe dysplasia. Likewise, presence of Hp-I in the CRC group was observed in 89% of patients with mild and 83% of patients with moderate/severe grade.5 Noteworthy, Hp presence was documented by immunohistochemical stain in CRA and CRC tissues.5 In addition, presence of Hp-I with accompanying immunohistochemical expression of CD44 (indicator of cancer stem cells [CSCs] and/or bone marrow-derived stem cells [BMDSCs]) in biopsy specimens was found in a high proportion of CRA patients accompanied with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%).5,6 Comparable pictures were also obtained for proliferation marker Ki-67, anti-apoptotic Bcl-2 and CD45 (assessing mainly T and B lymphocytes locally) immunohistochemical expressions.5,6

By introducing univariate analysis, the authors found that metabolic syndrome (MetS) was significantly associated with overall and advanced CRN.1 In this regard, in a systematic review, we reported an association between Hp-I and insulin resistance (IR), the major underlying mechanism responsible for the MetS.7 Our data further indicate that Hp-I might represent one further hit contributing to nonalcoholic fatty liver disease (NAFLD) pathogenesis, representing the hepatic component of MetS;8 NAFLD closely related to IR is involved in colon oncogenesis. Other studies also suggest that Hp-I with concomitant MetS might further increase CRA risk.9

Components of MetS are also associated with esophageal adenocarcinoma (EAC) risk and Hp-related IR7 might associated with gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE) and EAC.10 Although epidemiologic studies do not suggest causality with Hp, the interplay between Hp and host factors plays an important role in the pathogenesis of GERD and its complications BE and EAC in certain subpopulations.10

Therefore, casting further light in the uncertain pathophysiological mechanisms underlying Hp and CRN association, apart from gastrin mitogenic action mentioned by the aurhors,1 our results indicate that Hp-I has an impact on colorectal oncogenesis by: causing a possible chronic inflammatory mucosal damage, comparable to upper gastrointestinal tract (UGT); stimulating CSCs or recruiting BMDSCs, similar to UGT Hp-I-associated chronic inflammation, AG, hyperplasia, metaplasia, dysplasia and BMDSCs recruitment that may facilitate tumor formation and progression in animal models and humans;5,6 and affecting MetS parameters, oncogenes and immune surveillance processes, that may be involved in the sequence: colon epithelium transformation to CRA–dysplasia–CRC development/progression. Finally, Hp-related IR and additional MetS parameters might also contribute to GERD-BE-EAC sequence particularly in certain subpopulations,10 though further studies are warranted to elucidate the proposed mechanisms involved in Hp-induced colorectal and possibly UGT oncogenesis.

Therefore, Hp and MetS-related colon oncogenesis might justify CRN screening and surveillance program in the mentioned by the authors and by others high-risk patients9 and Hp eradication might inhibit the development or delay progression of CRN and possibly EAC.

References
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