RESUMEN
To verify the methylation status of THBS1, GPX3, and COX2 genes and to evaluate their association with Helicobacter pylori in gastric adenocarcinomas. Methylation-sensitive restriction enzyme PCR assay was performed in 16 diffuse type gastric cancer samples, 23 intestinal type, and 15 normal stomach tissue. The presence of H. pylori was performed by amplification of the fragment of the 16S rRNA. Statistical analyses were performed using Fisher's exact test. The hypermethylation of GPX3, THBS1, and COX2 occurred in 18 (n = 7), 5 (n = 2), and 36 % (n = 14) of gastric cancer samples, respectively, whereas in normal samples, it was found in 13, 7, and 67 %. The presence of H. pylori was detected in 67 % of gastric cancer samples and 67 % in normal gastric samples. The methylation of THBS1 and GPX3 was not significantly different between the types of tumors, normal sample, the presence of H. pylori, or clinicopathological variables studied (P > 0.05). However, the methylation status of the gene COX2 is significantly different between normal tissue and intestinal type gastric cancer (P = 0.02). Therefore, our results suggest that the methylation status of the gene COX2 is associated with the intestinal type of gastric cancer.
Asunto(s)
Ciclooxigenasa 2/genética , Glutatión Peroxidasa/genética , Neoplasias Intestinales/genética , Neoplasias Gástricas/genética , Brasil , Islas de CpG/genética , Metilación de ADN/genética , Femenino , Estudios de Asociación Genética , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/patogenicidad , Humanos , Neoplasias Intestinales/microbiología , Neoplasias Intestinales/patología , Masculino , Regiones Promotoras Genéticas , ARN Ribosómico 16S/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
Our study aimed to associate IL-1ß and IL-1RN polymorphisms with AD disease in comparison with elderly control group from São Paulo - Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and -511C>T and -31T>C (IL-1ß) polymorphisms. Our findings revealed that -511C/-31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas -511C/-31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population.
Asunto(s)
Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad , Haplotipos/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Polimorfismo Genético/genética , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite/genéticaRESUMEN
Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.