Resolving gastric cancer aetiology: an update in genetic predisposition

Lancet Gastroenterol Hepatol. 2018 Dec;3(12):874-883. doi: 10.1016/S2468-1253(18)30237-1.

Abstract

Every year gastric cancer accounts for nearly 1 million new cases and more than 720 000 deaths worldwide. Prognosis is dismal because most patients are diagnosed with advanced disease; as such, gastric cancer outcomes will benefit from better methods for identification of at-risk individuals that can be targeted for early detection. One approach to targeting high-risk populations is to identify individuals who are genetically predisposed to gastric cancer, as up to 15% of all patients report family history of the disease. On the basis of clinical manifestations, three gastric cancer syndromes have been described, but the diagnosis of some of these syndromes is suboptimal and could benefit from genetic information. Over the past decade, genome-wide association and next-generation sequencing studies have identified several low penetrance variants and high-risk genes, considerably increasing our understanding of inherited gastric cancer predisposition. From these studies, PALB2 has emerged as a new familial gastric cancer gene. Furthermore, genetic analyses in patients with sporadic gastric cancer suggest that more than 10% of all cases have pathogenic mutations, a finding of great importance for cancer aetiology. In this Review, we summarise the role of genetics in gastric cancer aetiology and the implications of genetics findings for the prevention of this malignancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age of Onset
  • Fanconi Anemia Complementation Group N Protein / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Mutation
  • Prognosis
  • Recombinational DNA Repair
  • Risk Factors
  • Sequence Analysis, DNA
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human