Genetic Instability in Gastric Cancer

Abstract

Gastric cancer remains a worldwide burden as a second leading cause of cancer death in both sexes (Globocan, 2011; Nobili et al., 2011). Although its incidence is in decline in developed countries, it is still the fourth most common malignancy in the world, behind cancers of the lung, breast, colon, and rectum (Globocan, 2011). The fall in its incidence is attributed mainly to the decline of the intestinal type of stomach cancer, whereas the incidence of the diffuse type has remained constant over time (Yamashita et al., 2011). On the other hand, there has been a progressive increase in the cardia and gastroesophageal junction adenocarcinoma (Milne et al., 2009; Yamashita et al., 2011). The exact cause of this shift in location is not known. The general decrease of gastric cancer frequency in developed countries is attributed to the changes in dietary habits and food preservation methods (Crew & Neugut, 2006; Kufe et al., 2003). The prevalence of gastric cancer varies throughout the world, with the highest rates reported in Korea, Japan, Central and South America, and Eastern Europe, whereas Western Europe, North America, Africa, Australia, and New Zealand are low incidence areas (Crew & Neugut, 2006; Tahara, 2008; Yamashita et al., 2011). Despite the decrease in its incidence and improvements in diagnosis, curative surgery, and treatment, gastric cancer remains major health burden due to its poor prognosis (Smith et al., 2006; Yamashita et al., 2011). Adenocarcinoma is the major histological type of gastric cancer; accounting for 90% to 95% of all gastric malignancies, and this chapter will focus only on this type of gastric tumours (Hamilton & Meltzer, 2006). Adenocarcinoma develops from the glandular cells of stomach mucosa, while other rare stomach cancers develop in lymph tissue (lymphoma), hormone – producing cells (carcinoid tumours), muscle cells (soft tissue sarcomas) or certain nerve cells (gastrointestinal stromal tumours or GIST) (Smith et al., 2006). Based on the widely used Lauren classification, adenocarcinomas are divided into two distinct pathological entities, intestinal and diffuse types, which have different clinicopathological and prognostic features (Yamashita et al., 2011). Intestinal type is associated with Helicobacter pylori infection, obesity and certain dietary factors, such as high intake of salt, smoked meats and food preserved with nitrites or nitrates, and is believed to arise through a long-term multistep progression from chronic gastritis to chronic atrophy to intestinal metaplasia to dysplasia (Crew & Neugut, 2006; Hamilton & Meltzer, 2006; Yamashita et al., 2011). Histologically it is well differentiated and occurs more commonly in older patients, males and blacks (Crew & Neugut, 2006). Diffuse type is poorly differentiated with infiltrating,