MicroRNAs in hereditary diffuse gastric cancer

Abstract

Abstract. In 2012, gastric cancer (GC) was the third cause of mortality due to cancer in men and women. In Central and South America, high mortality rates have been reported. A total of 95% of tumors developed in the stomach are of epithelial origin; thus, these are denominated adenocarcinomas of the stomach. Diverse classification systems have been established, among which two types of GC based on histological type and growth pattern have been described as follows: Intestinal (IGC) and diffuse (DGC). Approximately 1-3% of GC cases are associated with heredity. Hereditary-DGC (HDGC), with 80% penetrance, is an autosomal-type, dominant syndrome in which 40% of cases are carriers of diverse mutations of the CDH1 gene, which encodes for the cadherin protein. By contrast, microRNA are non-encoded, single-chain RNA molecules. These molecules regulate the majority of cellular functions at the post-transcriptional level. However, analysis of these interactions by means of Systems Biology has allowed the understanding of complex and heterogeneous diseases, such as cancer. These molecules are ubiquitous; however, their expression can be specific in different tissues either temporarily or permanently, depending on the stage of the cell. Due to the participation of microRNA in the processes of cellular proliferation, cell cycle control, apoptosis, differentiation and metabolism, these have been indicated to have a role in the development of cancerous processes, finding specific patterns of expression in different neoplasms, including GC, in which the microRNA expression profile is different in samples of non-cancerous versus cancerous tissues. A difference has been observed in the expression patterns of DGC and IGC. However, the role of microRNA in HDGC has not yet been established. The present study reviews the investigations that describe the participation of microRNA in the regulation of genes CDH1, RHOA, CTNNA1, INSR and TGF-β in different neoplasms, such as HDGC. Contents1. Introduction 2. Gastric cancer and heredity 3. Diffuse gastric cancer 4. MicroRNA in HDGC 5. HDGC and genes 6. Conclusion IntroductionCancer is the main cause of mortality in the world (8.2 million mortalities in 2012). Gastric cancer (GC) is estimated to be the fifth most common cancer worldwide, with 952,000 new cases annually. In 2012, GC was the third cause of mortality due to cancer in men and women; 70% of cases were reported in developing countries, with one-half of these in East Asia. In Central and South America, high mortality rates have been reported (1). In Mexico, according to the statistics of the National Institute of Statistics and Geography, the principal causes of mortalities due to neoplasms are those of the digestive tract organs (32.52 for every 100,000 inhabitants 20 years of age) (2).GC comprises any malignant neoplasm that originates from the region between the gastroesophageal junction and the pylorus. A total of 95% of tumors developed in the stomach are of epithelial origin; thus, these are denominated adenocarcinomas of ...

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