Understanding the genetic basis of gastric cancer: recent advances.

Two major gastric cancer histological subtypes are recognized with distinct morphology, epidemiology, pathogenesis and clinical behavior. Genetically, the intestinal and diffuse subtypes are also characterized by distinct germline susceptibility patterns and somatic aberrations. Helicobacter pylori is strongly associated with both Lauren's subtypes, although the underlying carcinogenic mechanisms are unique. Risk is modulated by strain-specific virulence factors, host responses and specific host-microbe interactions. Somatic aberrations in gastric cancer are driven by three major mechanisms, namely chromosomal instability, microsatellite instability and epigenetic alterations. These processes drive carcinogenesis in both Lauren's subtypes; however, the relative contribution of these processes and the specific genes aberrated differ. Moving beyond Lauren's subtypes, next-generation techniques have identified major genomic subtypes that have prognostic impact and exhibit distinct response patterns to standard cytotoxics.