Helicobacter pylori and Gastric Cancer

Helicobacter pylori has been the subject of intense investigation since its culture from a gastric biopsy in 1982. From the beginning, this gram-negative bacterium has provoked the interest of bacteriologists, gastroenterologists, infectious disease specialists, cancer biologists, epidemiologists, pathologists, and pharmaceutical scientists. Pathologists were among the first groups of scientists to reevaluate their data in the context of the newly discovered bacterial etiological agent. Chronic inflammation elicited by the bacterium provided the missing link in the progression to gastric carcinoma; accordingly, H. pylori was named as a class 1 carcinogen by the World Health Organization. Two key papers published in 1991 in the Journal of the National Cancer Institute reported a positive association between gastric cancer and H. pylori infection. This fact provided a strong rationale to treat all who tested positive for H. pylori. Antibiotic regimens have been largely successful, but some agents such as metronidazole and clarithromycin have been rendered ineffective in several countries and geographical areas of the United States by the emergence of strains resistant to these compounds. Although there was some skepticism initially, within few years numerous research groups verified the association of H.pylori with gastric carcinoma. Host related factors for the development of disease can indicate genetic susceptibility (or resistance) or acquired influences, which may stimulate defenses of the host against environmental carcinogens like H.pylori. The present article is a mini-review of the history and epidemiology of the bacterium and its suggested association with the development and progression of 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)(25)(26)(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 furazolidonebased 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)(32)(33).

COnCLUSiOn
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.

AUTHOR COnTRiBUTiOnS
ATB suggested the idea of writing the manuscript, finalized the same, and also approved the final version before submission.

ACKnOWLEDGMEnTS
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.