Understanding the genetic basis of gastric cancer: recent advances

Abstract

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.

Keywords::

• chromosomal instability
• epigenetics
• gastric cancer
• genetics
• intrinsic subtypes
• Lauren’s subtype
• microsatellite instability

Financial & competing interests disclosure

IB Tan and P Tan have a patent in application for the intrinsic gastric cancer gene signature. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.