Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2018; 24(43): 4928-4938
Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4928
Association between Helicobacter pylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas
Carolina Rosal Teixeira de Souza, Marcelli Carolini Alves Almeida, André Salim Khayat, Emerson Lucena da Silva, Paulo Cardoso Soares, Luiz Cláudio Chaves, Rommel Mario Rodríguez Burbano
Carolina Rosal Teixeira de Souza, Marcelli Carolini Alves Almeida, André Salim Khayat, Emerson Lucena da Silva, Rommel Mario Rodríguez Burbano, Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém, Pará 66075-110, Brazil
André Salim Khayat, Rommel Mario Rodríguez Burbano, Oncology Research Center, Federal University of Pará, João de Barros Barreto University Hospital, Belém, Pará 66073-000, Brazil
Paulo Cardoso Soares, Luiz Cláudio Chaves, Rommel Mario Rodríguez Burbano, Ophir Loyola Hospital, Belém, Pará 66060-281, Brazil
Author contributions: de Souza CR and Almeida MC contributed to this work equally, carried out the studies, collected the data, performed the statistical analysis and drafted the manuscript; Khayat AS performed the statistical analysis and participated in its design; da Silva EL performed the statistical analysis and drafted the manuscript; Soares PC, Chaves LC and Burbano RM participated in critical revision and editing of the manuscript; Burbano RM conceptualized and designed the study and helped to draft the manuscript; all authors read and approved the final manuscript.
Supported by the National Council for scientific and technological development, No. (CNPq) 402283/2013-9.
Institutional review board statement: This study was approved by the Ethics Committee of the João de Barros Barreto University Hospital in Belém, No. 142004 and No. 637.233.
Informed consent statement: Patients were not required to give informed consent for the publication because the study and analysis used anonymous data that were obtained after each patient agreed to the collection of pieces of the tumors by written consent.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The authors agree that if this manuscript is finally accepted for publication, the Copyright License Agreement will become effective immediately.
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: Carolina Rosal Teixeira de Souza, PhD, Adjunct Professor, Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, 1 - Guamá, Belém, Pará 66075-110, Brazil. carolrosalts@gmail.com
Telephone: +55-91-32018188 Fax: +55-91-32018188
Received: June 8, 2018
Peer-review started: June 8, 2018
First decision: July 4, 2018
Revised: September 11, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: November 21, 2018
Processing time: 166 Days and 10.1 Hours
Abstract
AIM

To correlate Helicobacter pylori (H. pylori), Epstein-Barr virus (EBV) and human papillomavirus (HPV) with gastric cancer (GC) cases in Pará State, Brazil.

METHODS

Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eber1 RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.

RESULTS

The majority of the 302 samples analyzed were obtained from men (65%) aged 55 years or older (67%) and were classified as the intestinal subtype (55%). All three pathogens were found in the samples analyzed in the present study (H. pylori: 87%, EBV: 20%, HPV: 3%). Overall, 78% of the H. pylori-positive (H. pylori+) samples were cagA+ (H. pylori-cagA+), and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA+ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.

CONCLUSION

HPV was not involved in gastric tumorigenesis. Prophylactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

Keywords: Gastric cancer; Gastric adenocarcinomas; Microorganisms; Helicobacter pylori; cagA; Epstein-Barr virus; Human papillomavirus

Core tip: We investigated the presence of Helicobacter pylori (H. pylori), Epstein-Barr virus (EBV) and human papillomavirus in gastric adenocarcinomas and their relationships with the clinicopathological characteristics of the patients. Despite the fact that all three pathogens were found in the samples, we believe that only H. pylori and EBV contribute to the transformation of tissue associated with carcinogenesis. A significant association between the cagA gene of H. pylori and EBV was also observed. Given this finding, the use of prophylactic and therapeutic measures against both H. pylori and EBV may help to prevent the development of gastric cancer, especially the more aggressive forms.