Determination of strains of Helicobacter pylori and of polymorphism in the interleukin-8 gene in patients with stomach cancer

Abstract

-Context -Gastric neoplasia is the second most common cause of death by cancer in the world and H. pylori is classified as a type I human carcinogen by the World Health Organization. However, despite the high prevalence of infection by H. pylori around the world, less than 3% of individuals carrying the bacteria develop gastric neoplasias. Such a fact indicates that evolution towards malignancy may be associated with bacterial factors in the host and the environment. Objectives -To investigate the association between polymorphism in the region promoting the IL-8 (-251) gene and the H. pylori genotype, based on the vacA alleles and the presence of the cagA gene, using clinical and histopathological data. Methods -In a prospective study, a total of 102 patients with stomach cancer and 103 healthy volunteers were analysed. Polymorphism in interleukin 8 (-251) was determined by the PCRrestriction fragment length polymorphism reaction and sequencing. PCR was used for genotyping the vacA alleles and the cagA in the bacterial strains PCR. Gastric biopsies were histologically assessed. Results -The H. pylori serology was positive for 101 (99%) of all patients analysed, and 98 (97%) of them were colonized by only one strain. In patients with monoinfection, 82 (84%) of the bacterial strains observed had the s1b/m1 genotype. The cagA gene was detected in 74 (73%) of patients infected by H. pylori. The presence of the cagA gene was demonstrated as associated with the presence of the s1b/m1 genotype of the vacA gene (P = 0.002).As for polymorphism in the interleukin 8 (-251) gene we observed that the AA (P = 0.026) and AT (P = 0.005) genotypes were most frequent in the group of patients with gastric adenocarcinoma. By comparing the different types of isolated bacterial strains with the interleukin -8 (-251) and the histopathological data we observed that carriers of the A allele (AT and AA) infected by virulent strains (m1s1 cagA+) demonstrated a greater risk of presenting a degree of inflammation (OR = 24.75 CI 95% 2.29-267.20 P = 0.004) and increased neutrophilic activity (OR = 28.71 CI 95% 2.62-314 P = 0.002) in the gastric mucosa. Conclusion -Our results demonstrate that the interaction between polymorphism in the interleukin -8 (-251) gene, particularly with carriers of the A allele and the infecting type of H. pylori strain (s1m1 cagA positive) performs an important function in development of gastric adenocarcinoma.

Case study of stomach adenocarcinoma conducted at a cancer referral hospital in northern Brazil

“…Evaluation of the origin of the patients according to mesoregion showed that most patients of this study were from the metropolitan region of Belém, followed by patients from the Northeastern region of the state. This high incidence of gastric adenocarcinoma in these two mesoregions agrees with epidemiological studies, which have shown that the large number of cases seen in the metropolitan area of Belém is associated with the large size of the population living in this region, in addition to dietary habits and a high prevalence of infection with Helicobacter pylori (9,28,37) . In the Northeastern region, an intimate association has been demonstrated between the use of brine for food preservation and an increased risk of gastric carcinogenesis (28) .…”

“…This finding might be explained by the etiopathogenesis of gastric adenocarcinoma of the intestinal type, which is characterized by atrophic gastritis and intestinal metaplasia and involves factors such as dietary habits, exposure to H. pylori and smoking that share the preference for distal portions of the stomach (5,13,14,19,36) . Other studies have demonstrated the participation of these factors in the etiopathogenesis of gastric adenocarcinoma in the State of Pará (9,25,27,28,37) . Macroscopic analysis showed that most cases were advanced tumors, with the observation of a larger number of ulcerated-infiltrative lesions (Borrmann III), followed by ulcerated and delimited lesions (Borrmann II).…”

“…In addition, studies have shown a high prevalence of infection with Helicobacter pylori among patients with gastric adenocarcinoma from the State of Pará (25,37) . Taken together, these factors may explain the high incidence of gastric cancer in this region.…”

Chemokines, chemokine receptors and the gastrointestinal system

“…They predicted that the CXCL8 251 AA genotype may be associated with angiogenesis in gastric carcinogenesis in the H. pylori-infected population. Vinagre et al [134] reported that interaction between CXCL8 251 (AA and AT) allele mutation carriers and the infection of H. pylori strain [phosphoinositide PI4, 5P(2) binding protein (s1m1) cytotoxin-associated gene A product (cagA) positive] may have higher risk for development of gastric adenocarcinoma. In addition, Schneider et al [135] pointed out the complexity and difficulty in selecting in vitro epithelial study models to understand the molecular mechanisms of H. pylori infection.…”

“…Enhancement of tumor development factors, and a possible risk factor as mutant, association with angiogenesis, development of gastric adenocarcinoma [132][133][134]183] …”