Estresse oxidativo e genótipo do H. pylori em pacientes portadores de câncer gástrico e seus familiares

Abstract

Gastric cancer is associated with H. pylori infection, environmental factors and genetic predisposition. Relatives of gastric cancer patients are at increased risk to develop cancer, possibly, due to infection by more virulent H. pylori strains and genetic predisposition associated with pro-inflammatory cytokines, which may, in turn, result in an exaggerated inflammatory response and oxidative stress. The aim of this study was to: 1) evaluate the oxidative stress in dispeptic patients without family history of gastric cancer (NRC), patients with gastric cancer (GC) and relatives of gastric cancer (RC); 2) evaluate the prevalence of the H. pylori genotypes homA, homB and cagE in RC and NRC and determine if the cagE gene is associated with GC as well as the pattern of cagA EPYIA phosphorylation in GC. This study was performed at the Hospital Universitário Walter Cantídeo (HUWC) in Fortaleza. Blood samples were collected and centrifuged to obtain serum, in order to measure the concentration of reduced glutathione (GSH), an anti-oxidant, and Malondealdehyde (MDA), a product of lipid peroxidation. DNA extraction was performed in gastric biopsies, followed by PCR and electrophoresis for ureA, vacA, homA, homB, cagA e cagE genes. The concentrations of MDA and GSH were evaluated in 213 patients (54 CG, 91 RC e 68 NRC). The group of CG had higher MDA and lower GSH concentrations when compared to the groups without cancer (p=0.001 and p=0.005, respectively). The H. pylori genotypes were evaluated in 186 patients (48 CG, 74 RC and 64 NRC). The overall cagE prevalence was 54.3% (101/186), 70% (52/74) in the RC group, 52% (25/48) in the GC group and 36% (24/87) in the NRC group. A significant and independent association was found between the cagE genotype and the RC group (OR 3,357; IC 2,026 - 9,476 95%: p=0,001) and between the homB genotype and the RC group (OR (OR 2,357; IC 95%: 1,401 – 3,961; p=0,001). Forty six cagA positive samples from the GC group were included for gene sequencing to evaluate the EPIYA phosphorylation sites of the CagA protein. All of the strains studied had an EPIYA-C pattern and approximately 50% of the strains were mixed. This study demonstrates that patients with gastric cancer are under higher levels of oxidative stress. The group of RC have a higher prevalence of cagE and homB. The group of GC patients had a high prevalence of mixed strains regarding CagA EPIYA-C phosphorylation pattern. Decreasing the lipid peroxidation, increasing the antioxidant reserve and identifying groups at risk of infection with more virulent strains of H. pylori may be important to prevent gastric cancer.