Tumour suppressor genes in gastric carcinogenesis: an up-to-date review of genetic and epigenetic changes in the development of gastric adenocarcinoma

Gastric cancer is the fifth commonest cancer worldwide and is the third leading cause of cancer related death. The 5-year survival rate is just 20%, partly as a consequence of our limited understanding of the pathogenesis of gastric cancer. Tumour suppressor genes (TSGs) play an important protective role in preventing the malignant transformation of cells by repairing DNA, inhibiting cell proliferation and initiating programmed cell death. Over recent decades there has been a rapid expansion in the number of TSGs that have been identified in relation to gastric adenocarcinoma and it is hoped that these may act as biomarkers of disease or provide potential therapeutic targets. Mutations in TSGs, oncogene activation and epigenetic change have all been shown to participate in gastric carcinogenesis. Here we discuss some of the key TSGs implicated in the development of gastric adenocarcinoma and present an up-to-date review of what is currently understood about the genetic and epigenetic alterations of tumour suppressors that underpin gastric carcinogenesis.