Evaluation of polymorphisms of genes involved in the inflammatory process induced by Helicobacter pylori in the stomach carcinogenesis

• Grant number: 10/00507-0
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2010
• End date: March 31, 2012
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ana Elizabete Silva
• Grantee: Ana Elizabete Silva
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated researchers: Juliana Garcia de Oliveira Cucolo ; Yvana Cristina Jorge

Abstract

Molecular epidemiology studies have highlighted the association of genetic polymorphisms with increased risk for developing different types of cancers such as gastric cancer. The main etiologic factor responsible for the inflammatory process that acts as a trigger of cellular and molecular changes in the gastric epithelium is infection with H. pylori. Although this bacterium colonize approximately 50% of world population, it is believed that both virulence factors of the parasite as differences in the host immune response are associated with risk of malignant progression of gastric cancer. The increase of risk is also associated with environmental factors such as diet, smoking and alcoholism. The interaction between these genetic variants and environmental factors may determine increased individual susceptibility to development of this malignancy. The polymorphisms of genes for factors involved in the inflammatory process, which can modulate the pattern of the host immune response, such as polymorphisms in regulatory and functional regions of cytokines genes and some receptors, which may alter the rates of transcription and expression levels of proteins. Therefore, we selected a group of 19 polymorphisms in 10 genes associated with the inflammatory process as NOS2 and COX-2, and as the host immune response genes of pro-inflammatory cytokines (IL-1b, IL-8, TNF-a and TNF-b), anti-inflammatory (IL-10 and IL1-RN) and receptors for recognition of molecular patterns associated with microbes, known as Toll like receptor (TLR2 and TLR4). Thus, we evaluate by PCR/RFLP and PCR-specific allele techniques the frequencies and association of these polymorphisms in susceptibility to chronic gastritis and gastric cancer in a sample of the Brazilian population. We will also investigate the interaction of these polymorphisms with environmental factors, especially the infection by H. pylori and smoking and alcohol habits. In a subgroup of patients with cancer and gastritis also evaluated the levels of expression of mRNA in gastric mucosa of the genes IL-8, IL-10 and TNF-a, whose polymorphisms occur in the promoting regions, by real-time PCR technique to verify if these polymorphisms alter the levels of gene expression. The study is inedited and important because there are no publications involving a combined analysis of this group of genes related to inflammatory process and immune response, specifically in these diseases. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GARCIA OLIVEIRA, J.; CRISTINA DUARTE, M.; ELIZABETE SILVA, A.. IL-1ra anti-inflammatory cytokine polymorphism is associated with risk of gastric cancer and chronic gastritis in a Brazilian population, but the TNF-beta pro-inflammatory cytokine is not. MOLECULAR BIOLOGY REPORTS, v. 39, n. 7, p. 7617-7625, JUL 2012. (10/00507-0)

DE OLIVEIRA, JULIANA GARCIA; TEIXEIRA ROSSI, ANA FLAVIA; NIZATO, DANIELA MANCHINI; MIYASAKI, KENJI; SILVA, ANA ELIZABETE. Profiles of Gene Polymorphisms in Cytokines and Toll-Like Receptors with Higher Risk for Gastric Cancer. Digestive Diseases and Sciences, v. 58, n. 4, p. 978-988, APR 2013. (10/00507-0)

DE OLIVEIRA, JULIANA GARCIA; TEIXEIRA ROSSI, ANA FLAVIA; NIZATO, DANIELA MANCHINI; TARGA CADAMURO, ALINE CRISTINA; JORGE, YVANA CRISTINA; VALSECHI, MARINA CURADO; RODRIGUES VENANCIO, LARISSA PAOLA; RAHAL, PAULA; PAVARINO, ERIKA CRISTINA; GOLONI-BERTOLLO, ENY MARIA; et al. Influence of functional polymorphisms in TNF-alpha, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer. TUMOR BIOLOGY, v. 36, n. 12, p. 9159-9170, DEC 2015. (10/00507-0)

JORGE, YVANA C.; DUARTE, MARCIA C.; SILVA, ANA E.. Gastric cancer is associated with NOS2-954G/C polymorphism and environmental factors in a Brazilian population. BMC GASTROENTEROLOGY, v. 10, JUN 17 2010. (10/00507-0)

DE OLIVEIRA, JULIANA GARCIA; SILVA, ANA ELIZABETE. Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population. WORLD JOURNAL OF GASTROENTEROLOGY, v. 18, n. 11, p. 1235-1242, MAR 21 2012. (10/00507-0)