RESUMO
Objetivo: Evaluar la asociación de los polimorfismos de alguna de las citocinas más estudiadas en relación con el cáncer gástrico (IL-1B-511, IL-1RN intron-2-VNTR, TNF-α-308, IL-10-819 e IL-10- 1082) y la presencia de anticuerpos hacia la proteína cagA de Helicobacter pylori con las lesiones preneoplásicas gástricas en pacientes colombianos. Materiales y métodos: Se estudiaron 185 pacientes con lesiones preneoplásicas (gastritis atrófca, metaplasia intestinal y displasia), y 154 controles (gastritis no atrófica), provenientes de hospitales de una zona de riesgo alto y otra de riesgo bajo para cáncer gástrico. Se obtuvieron biopsias gástricas y muestras de sangre; la genotipificación de los polimorfismos se hizo por discriminación alélica usando PCR en tiempo real y por PCR convencional y electroforesis en agarosa (VNTR del intron 2 de IL-1RN); la serología de Helicobacter pylori y Helicobacter pylori cagA se determinó por ELISA. Se utilizó regresión logística multinomial en el análisis estadístico. Resultados: El genotipo IL-1B-511TT (odds ratio = 4,05; intervalo de confianza 95% 1,35-12,10) se asoció a metaplasia intestinal; no se observaron otras asociaciones entre los diferentes polimorfismos y las lesiones preneoplásicas. La infección por Helicobacter pylori cagA positivo se asoció a gastritis atrófica, metaplasia intestinal y displasia (OR = 2,66; 13,70; 40,29, respectivamente). Conclusión: Los resultados sugieren que entre los genotipos proinflamatorios el genotipo IL-1B-511TT estaría asociado a la metaplasia intestinal, y la serología de Helicobacter pylori cagA positivo sería un biomarcador útil para intervenir y prevenir la presencia de lesiones preneoplásicas. Se necesitan otros estudios con población colombiana que evalúen la asociación hallada de IL1B-511 con la metaplasia intestinal.
Objective: To evaluate the relationship of some of the most studied cytokines (IL-1B-511, IL-1RN intron-2-VNTR, TNF-a-308, IL-10-819, and IL-10-1082) with gastric cancer, as well as the presence of anti-Helicobacter pylori cagA IgG antibodies with pre-cancerous lesions in Colombian patients. Materials and methods: A study was conducted on 185 patients with pre-cancerous lesions (atrophic gastritis, intestinal metaplasia and dysplasia), and 154 controls (non-atrophic gastritis), seen in hospitals in a high risk area, and another in a low risk area, for gastric cancer. Gastric biopsy specimens and blood samples were obtained. The genotyping of the polymorphisms was performed by allelic discrimination using real-time PCR, conventional PCR, and agarose electrophoresis (VNTR of IL-1RN intron 2). The serology of Helicobacter pylori and Helicobacter pylori cagA was determined by ELISA. A multinomial logistic regression was used in the statistical analysis. Results: The IL-1B-511TT genotype was associated with intestinal metaplasia (OR=4.05; 95% CI; 1.35-12.10). No other relationships were observed between the different polymorphisms and preimg/revistas/rcc/cancerous lesions. Infection due to a positive Helicobacter pylori cagA was associated with atrophic gastritis, intestinal metaplasia and dysplasia (OR=2.66; 13.70; 40.29, respectively). Conclusion: The results suggest that, among the pro-inflammatory genotypes, the IL-1B-511TT would be associated with intestinal metaplasia, and that a positive Helicobacter pylori cagA serology could be a useful biomarker for the intervention and prevention of pre-cancerous lesions. Further studies are required in the Colombian population in order to evaluate the relationship found between IL1B-511 and intestinal metaplasia.
Assuntos
Humanos , Lesões Pré-Cancerosas , Neoplasias Gástricas , Helicobacter pylori , Interleucina-10 , Sangue , Imunoglobulina G , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Background: There is an association of interleukin (IL)1B polymorphism with gastric cancer risk. However systematic reviews of the existing evidence have shown that such association varies across populations with different genetic ancestry. Aim: To evaluate the association of IL-1B-511 and IL-1RN polymorphism and Helicobacter pylori IgG antibodies CagA, with gastric cancer in two Colombian cities located in a high risk area for gastric cancer. Material and Methods: A case-control study including 46 gastric cancer cases and 99 controls with non-atrophic gastritis from a high risk zone for gastric cancer. Polymorphism genotyping was carried out by polymerase chain reaction (PCR) and IgG CagA status by ELISA. Results: IgG CagA seropositive individuals had an increased gastric cancer risk (odds ratio (OR) = 11.56; 95 percent confidence intervals (CI) 2.62-50.91 in Tunja and OR = 19.66, 95 percentCI 0.98-395 in Bogotá). IL-1B-511TT carriers in Tunja had increased risk of gastric cancer (OR = 11.31; 95 percentCI 1.20-106.54)), while IL-1RN*2 alelle carriers in Bogotá showed an inverse association with gastric cancer risk (OR = 0.03; 95 percentCI 0.01-0.65). Conclusions: This study adds evidence to the positive association of Helicobacter pylori CagA positive strains with non-cardial gastric cancer etiology. There is a possible heterogeneity in the association of IL-1B gene polymorphism with cancer, in populations of similar ethnic background and settled in the same risk area.