[Hereditary gastric cancer. Genetics and clinical management]

Recently, germline mutations in the E-cadherin/CDH1 gene have been identified in families with an autosomal-dominant inherited predisposition to gastric cancer of the diffuse type. Criteria to define familial gastric cancer syndromes have been proposed and include review of the histopathology and pedigree analysis of any family with an aggregation of gastric cancer cases. Of families with two or more cases of diffuse gastric cancer in first- or second-degree relatives < 50 years of age or three or more cases at any age, up to half may be attributable to inherited germline mutations in the E-cadherin/CDH1 gene. Cumulative lifetime risk of developing gastric cancer in CDH1 mutation carriers is 70%, women from these families also have increased risk for developing lobular breast cancer. Prophylactic gastrectomies have been performed in several unaffected CDH1 mutation carriers; despite normal endoscopic examinations and negative gastric biopsy specimens, pathologic foci of early gastric cancer were found in all surgical specimens. Based on these results, guidelines for genetic testing, counseling and management of individuals with hereditary diffuse gastric cancer have been proposed. Raised awareness among the physician community regarding this syndrome may allow for increased detection and prevention of gastric and breast cancers in these high-risk individuals.