Role of Gastrokine 1 in Gastric Cancer

Gastric cancer (GC) has high incidence (> 1.000.000 new cases/year) and mortality rate in several countries and is still one of the most frequent and lethal (> 600.000 dead/year) neoplasia with an average surviving of five years (less than 20%) (Pisani et al., 1990; Lands et al., 1998). It is already well known that infection of gastric antrum mucosal with the bacterium Helicobacter pylori is the cause of the chronic inflammation that leads to intestinal-type gastric cancer in the majority of the cases. The H. pylori infection is widespread but only a small number of the total population of infected individuals might eventually develop adenocarcinoma (around 3/10,000 individuals per year or 2.1% for lifetime infection) 27 (Correa & Piazuelo, 2008). Risk factors influencing the outcome of H. pylori–associated pathology include bacterial cytotoxic heterogeneity, diet, and geographic differences. The phenomenon of decreased gastric cancer incidence in Africa compared with other regions where H. pylori is endemic 28 (Holcombe, 1992) is probably due to the different diet of these populations compared to the western countries. This discrepancy has been partially attributed to helminth co-infection that likely modifies the characteristic proinflammatory type 1 T-helper 1 cell response, to a T-helper 2–predominant response 29 (Whary et al., 2005), typified by the release of non-inflammatory cytokines and reduced incidence of H. pylori–associated glandular atrophy, an early marker of cancer development. The identification of novel genes regulated by H. pylori in vivo, particularly those contributing to these early stages of gastric cancer, would facilitate improved understanding of the differential susceptibility to this pathogen. The different susceptibility among individuals to H. pylori infection is still not yet defined. Some works, however, suggested that the polymorphisms in host genetic factors like the proinflammatory cytokines interleukin-1, interleukin-8, and tumor necrosis factor may play a relevant role 30 (El-Omar et al., 2003). The evolution of intestinal tumours is characterized by a progression of several sequential steps that starts with gastritis and then progresses to mucosal atrophy (atrophic gastritis), intestinal metaplasia, dysplasia and carcinoma with subsequent metastatic dissemination (Correa, 1992, 1995). The diffuse-type has instead a poorer prognosis and develops through unknown genetic and morphological events from normal gastric epithelium. No preceding steps have been identi_ed in the pathogenesis of diffuse carcinoma other than the chronic gastritis. The pathogenesis of gastric cancer remains poorly understood although it is evident that several environmental factors, such as H. pylori infection can be one of the causes leading to this disease. In fact, the risk to develop gastric cancer is increased in patients with H. pylori infections probably as the result of a combination of genetic and environmental factors in which the infection by H. pylori is of particular relevance, especially when the inflammation involves the gastric body region with respect to the antrum (Correa, 1995; Goldstone et al., 1996; Nabewera & Logan, 1999). Generally, this condition is associated to different degrees of atrophy and alterations of the secretor function that, in the long term, became associated to gastric carcinoma (Forman et al., 1991; Parsonnet et al., 1997; Watanabe et al., 1998). Diffuse adenocarcinoma shows an increased propensity for intra and transmural spread and is therefore associated with a poorer prognosis. Unfortunately, the histological classification of an individual gastric adenocarcinoma is not clear-cut with a tumour often comprising a mixture of intestinal and diffuse tissue types. Under these considerations, we think that there is an urgent necessity to dispose of an efficient tool for the detection of early stage gastric cancer like the identification of highly sensitive and specific biomarkers that will aid disease diagnosis and ensure early clinical intervention, thereby preventing mortality and reducing morbidity (Boussioutas & Taupin, 2001). Since most of GC (around 73%) is developed at antrum/pylorus, proteins secreted by antrum/pylorus mucosa might play a critical role in maintaining normal gastric mucosa structure and function