Familial gastric cancer: detection of a hereditary cause helps to understand its etiology

Ingrid P Vogelaar,Marjolijn Jl Ligtenberg,J Han Jm Van Krieken,Rachel S Van Der Post,Tanya M Bisseling,Nicoline Hoogerbrugge

doi:10.1186/1897-4287-10-18

Abstract

Worldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality. Several environmental factors predispose to the development of gastric cancer, such as Helicobacter pylori infection, diet and smoking. Familial clustering of gastric cancer is seen in 10% of cases, and approximately 3% of gastric cancer cases arise in the setting of hereditary diffuse gastric cancer (HDGC). In families with HDGC, gastric cancer presents at relatively young age. Germline mutations in the CDH1 gene are the major cause of HDGC and are identified in approximately 25-50% of families which fulfill strict criteria. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. However, in the majority of families with multiple cases of gastric cancer no germline genetic abnormality can be identified and therefore preventive measures are not available, except for general lifestyle advice. Future research should focus on identifying new genetic predisposing factors for all types of familial gastric cancer.

Highlights

Worldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality
Environmental factors are mainly involved in the etiology of the intestinal type of gastric cancer (GC)
A large systematic review of 42 studies showed that the risk of GC is increased by 60% in male and 20% in female smokers compared to never smokers [12]

Summary

Conclusion

The overall incidence of GC is declining, which is most likely due to the reduction in environmental risk factors. Germline mutations in the CDH1 gene have been identified as an important cause of HDGC, but still in more than two thirds of strictly selected HDGC families the genetic cause remains unknown. The genetic basis of familial cases with an intestinal type gastric cancer is largely unknown. Elucidation of novel gastric cancer susceptibility genes will be an important step towards additional options for gastric cancer prevention. Identifying new genetic gastric cancer predisposing factors is one of the important targets in the near future. All authors read and approved the final manuscript. Author details 1Department of Human Genetics, Radboud University Nijmegen Medical Centre, PO box 9101, Nijmegen 6500HB, The Netherlands. Author details 1Department of Human Genetics, Radboud University Nijmegen Medical Centre, PO box 9101, Nijmegen 6500HB, The Netherlands. 2Department of Pathology, Radboud University Nijmegen Medical Centre, PO box 9101, Nijmegen 6500HB, The Netherlands. 3Department of Gastroenterology, Radboud University Nijmegen Medical Centre, PO box 9101, Nijmegen 6500HB, The Netherlands

Helicobacter and Cancer Collaborative Group

Findings

28. Friedenson B