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Role of gene polymorphisms in gastric cancer and its precursor lesions:Current knowledge and perspectives in Latin American countries

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World Journal of Gastroenterology 2014年第16期20卷 4503-4515页

作者： miguel angel chiurillo Laboratorio de Genética Molecular "Dr.Jorge Yunis-Turbay" Decanato de Ciencias de la SaludUniversidad Centroccidental Lisandro AlvaradoBarquisimeto 3001Venezuela

Latin America shows one of the highest incidence rates of gastric cancer in the world,with variations in mortality rates among nations or even within countries belonging to this *** cancer is the result of a multifactorial complex process,for which a multistep model of carcinogenesis is currently *** to the infection with Helicobacter pylori,that plays a major role,environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer *** differences in population origin,demographic structure,socio-economic development,and the impact of globalization lifestyles experienced in Latin America in the last decades,all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric *** aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world.A total of 40 genes or genomic regions and69 genetic variants,58%representing markers involved in inflammatory response,have been used in a number of studies in which predominates a low number of individuals(cases and controls)*** of IL-1B(-511 C/T,14 studies;-31 T/C,10 studies)and IL-1RN(variable number of tandem repeats,17 studies)are the most represented ones in the reviewed *** genetic variants recently evaluated in large metaanalyses and associated with gastric cancer risk were also analyzed in a few studies[e.g.,prostate stem cell antigen(PSCA),CDH1,Survivin].Further and better analysis centered in gene polymorphisms linked to other covariates,epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of gastric cancer etiology in order to d

关键词： Latin America Gastric cancer Precancerous lesions Gene polymorphisms Single nucleotide polymorphisms

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TCF7L2 rs7903146 polymorphism is associated with gastric cancer: a case-control study in the Venezuelan population

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World Journal of Gastroenterology 2016年第28期22卷 6520-6526页

作者： Keila Torres Luis Labrador Elvis Valderrama miguel angel chiurillo Laboratorio de Genetica Molecular 'Dr. Jorge Yunis-Turbay' Decanato de Ciencias de la Salud Universidad Centroccidental Lisandro Alvarado Barquisimeto 3001 Venezuela Postgrado en Ciencias Biologicas Departamento de Biologia Celular Universidad Simon Bolivar Caracas 1081-A Venezuela Departamento de Anatomia Patologia Hospital Antonio Maria Pineda-UCLA Barquisimeto 3001 Venezuela Departamento de Patologia Clinica Universidade Estadual de Campinas Campinas 13083 Sao Paulo Brazil

AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan ***: We performed a case-control study including 122 paraffin-embedded archived intestinal-type gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene (rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined. Statistic powers were post-hoc ***: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model (OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele (CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer (dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model (OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric ***: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.

关键词： Gastric cancer Wnt/β -catenin pathway TCF7L2 Single nucleotide polymorphism Genetic susceptibility

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Role of the Wnt/β-catenin pathway in gastric cancer: An indepth literature review

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World Journal of Experimental Medicine 2015年第2期5卷 84-102页

作者： miguel angel chiurillo Laboratorio de Genética Molecular "Dr. Yunis-Turbay" Decanato de Ciencias de la Salud Universidad Centroccidental Lisandro Alvarado Departamento de Patologia Clínica Universidade Estadual de Campinas

Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal *** aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/b-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors(mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.

关键词： Gastric cancer Wnt β-catenin Oncogene Tumor suppressor Epigenetics Helicobacter pylori Adenomatous polyposis coli

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