Helicobacter pylori and Gastric Cancer
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Helicobacter pylori: State of the Art
Existence of any infectious agents in stomach was a big query among the microbiologists and gastroenterologists (1–3). Helicobacter pylori (H. pylori) is a leading cause of severe digestive disease, including gastric cancer (4, 5). Although over the last years, incidence of gastric carcinoma is decreasing worldwide, it remains the fourth most common cancer and the second most common cause of malignancy-related death worldwide (6, 7). During the years after H. pylori discovery, especially following many meta-analyses and certain number of experimental evidences, it became a crucial question whether there is a link between gastric cancer and H. pylori infection (8). A contributory role for H. pylori in gastric cancer was first announced by the International Agency for Research on Cancer (IARC), when they labeled H. pylori a class I carcinogen (9). Moreover, since the prevalence of H. pylori and pattern of superficial gastritis can change quickly within a specific population, the incidence of gastric cancer can also shift rapidly (10). It has been generally accepted that the risk of cancer is highest among patients in whom the primary colonization causes acute and then chronic inflammation (11). To our knowledge, certain H. pylori strains seem to differently increase the risk of cancer, depending on the existence of certain bacterial genotypes (for example: cagA) (12, 13). Bacterial-secreted CagA, inducing high levels of chronic inflammation, is the main factor increasing mutagenesis rate, oxidative-stress, and increased mismatch repair pathways, resulting in gastric carcinogenesis (14, 15). Hence, both prevalence and incidence rates are different in various geographical areas (16, 17). Taking together, in this paper, we aim to point out all important topics concerning management of H. pylori strains associated with gastric cancer.
Prevention of Gastric Cancer
To now, prevention is an optimal approach to deal with gastric cancer. Thus, all choices ending in elimination of the H. pylori would be on the desk. Unfortunately, we do not have any preventive or therapeutic vaccine against the infection, but ongoing research is trying to find the best solution (18). Using metagenomic experiments can help scientists to determine properties of each microbiota member, which contributes in pathogenesis of gastric cancer. The molecular mechanism of the interaction between gastric epithelial cells and H. pylori may also suggest a novel strategy for effective prevention of the development of gastric cancer (19, 20). Considering genetical background bound to high risk of gastric cancer, it is a major recommendation to eradicate H. pylori in persons with a family history of gastric cancer (21, 22). Further studies are necessary to elucidate actual role of H. pylori as causative agent to the development of gastric cancer.
H. pylori and Antibiotic Resistance
Overall, H. pylori resistance to antibiotics, including clarithromycin and metronidazole, has increased during the last years; new therapeutic regimens are required in both national and global levels (23). Although a large number of therapeutic regimens are available, none had proven to be superior. Thus, effective country-based antibiotic therapy programs should be continued, especially in high prevalence regions, such as India and Iran (24–27). According to the latest Maastricht Guidelines, in regions of low clarithromycin resistance (<15%), clarithromycin-containing treatments are recommended for first-line therapy (28). So far, in regions with high resistance to clarithromycin (>15%), the quadruple treatment, including bismuth, has been proposed as first-line treatment. Sequential therapy [non-bismuth (three antibiotics plus proton pump inhibitors) quadruple therapy] was recommended in the case of unavailability of the above therapy. The third-line therapy of H. pylori is another challenging topic in treatment of this infection. Now, most of international guidelines suggest that patients requiring third-line therapy should be advised to the antibiotic susceptibility test before prescribing. However, an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be applied if antimicrobial sensitivity data are not ready.
Existence of the Virulent Bacterium
H. pylori infection is thought to be acquired in early childhood mostly with the fecal–oral mode of transmission (29, 30). In order to answer how only a few among those with H. pylori infection develop gastric cancer, it has been proposed that there are highly specific strains of H. pylori, called “virulent bacterium,” carrying certain genotypes of cagA (1). Of interest, current knowledge elucidating the etiologic role of the H. pylori CagA in gastric cancer is lacking (31–33).
Gastric cancer induced by H. pylori is one of the malignancies associated with inflammation (34). Extensive epidemiologic studies showed that H. pylori eradication reduces bacterial effects relevant to the gastric cancer (35). The passed direction of H. pylori and gastric cancer research indicating on a shared line which should be well-established following next investigations. To date, existing findings indicate that gastric cancer is the biologic translation of carrying an infectious disease, which is interestingly preventive with anti-H. pylori regimen (36, 37). Therefore, as an inevitable consequence, identification of H. pylori colonized in people with high risk of gastric cancer is the main direction of the future research.
ATB suggested the idea of writing the manuscript, finalized the same, and also approved the final version before submission.
Conflict of Interest Statement
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The contents of the paper are the sole responsibility of the author and do not necessarily represent the official views of any institute or organization.
4. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med (1991) 325(16):1127–31. doi:10.1056/NEJM199110173251603
7. Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, et al. Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory. Eur J Cancer (2015) 51(9):1164–87. doi:10.1016/j.ejca.2013.09.002
8. Abadi ATB, Taghvaei T, Mobarez AM, Vaira G, Vaira D. High correlation of babA 2-positive strains of Helicobacter pylori with the presence of gastric cancer. Intern Emerg Med (2013) 8(6):497–501. doi:10.1007/s11739-011-0631-6
12. Ferreira RM, Pinto-Ribeiro I, Wen X, Marcos-Pinto R, Dinis-Ribeiro M, Carneiro F, et al. Helicobacter pylori cagA promoter region sequences influence cagA expression and interleukin 8 secretion. J Infect Dis (2016) 213(4):669–73. doi:10.1093/infdis/jiv467
15. Cortes MC, Yamakawa A, Casingal CR, Fajardo LS, Juan ML, De Guzman BB, et al. Diversity of the cagA gene of Helicobacter pylori strains from patients with gastroduodenal diseases in the Philippines. FEMS Immunol Med Microbiol (2010) 60(1):90–7. doi:10.1111/j.1574-695X.2010.00722.x
17. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol (2006) 24(14):2137–50. doi:10.1200/JCO.2005.05.2308
22. Lai KC, Lam SK, Chu KM, Wong BC, Hui WM, Hu WH, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med (2002) 346(26):2033–8. doi:10.1056/NEJMoa012877
23. Haghi Tomatari F, Mohabbati Mobarez A, Amini M, Hosseini D, Talebi Bezmin Abadi A. Helicobacter pylori resistance to metronidazole and clarithromycin in dyspeptic patients in Iran. Iran Red Crescent Med J (2010) 12(4):409–12.
24. Abadi ATB, Taghvaei T, Mobarez AM, Carpenter BM, Merrell DS. Frequency of antibiotic resistance in Helicobacter pylori strains isolated from the northern population of Iran. J Microbiol (2011) 49(6):987–93. doi:10.1007/s12275-011-1170-6
28. Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infection – the Maastricht IV/Florence consensus report. Gut (2012) 61(5):646–64. doi:10.1136/gutjnl-2012-302084
30. Rothenbacher D, Winkler M, Gonser T, Adler G, Brenner H. Role of infected parents in transmission of Helicobacter pylori to their children. Pediatr Infect Dis J (2002) 21(7):674–9. doi:10.1097/00006454-200207000-00014
31. Umehara S, Higashi H, Ohnishi N, Asaka M, Hatakeyama M. Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. Oncogene (2003) 22(51):8337–42. doi:10.1038/sj.onc.1207028
32. Truong BX, Mai VTC, Tanaka H, Thong TM, Hai HH, Van Long D, et al. Diverse characteristics of the CagA gene of Helicobacter pylori strains collected from patients from southern Vietnam with gastric cancer and peptic ulcer. J Clin Microbiol (2009) 47(12):4021–8. doi:10.1128/JCM.00504-09
33. Talebi Bezmin Abadi A, Mobarez AM, Bonten MJM, Wagenaar JA, Kusters JG. Clinical relevance of the cagA, tnpA and tnpB genes in Helicobacter pylori. BMC Gastroenterol (2014) 14:33. doi:10.1186/1471-230X-14-33
Keywords: Helicobacter pylori, gastric cancer, research directions
Citation: Talebi Bezmin Abadi A (2016) Helicobacter pylori and Gastric Cancer. Front. Med. 3:36. doi: 10.3389/fmed.2016.00036
Received: 17 June 2016; Accepted: 05 August 2016;
Published: 22 August 2016
Edited by:Arun Chaudhury, GIM Foundation, USA
Reviewed by:Vijaya Sena Reddy Dendi, The Wright Center for Graduate Medical Education, USA
Chitharanjan Duvoor, University of Arkansas for Medical Sciences, USA
Copyright: © 2016 Talebi Bezmin Abadi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Amin Talebi Bezmin Abadi, email@example.com