Hereditary gastric cancer. Indications of genetic study. When and to whom?

Abstract

The aim is to update the current knowledge in hereditary gastric cancer, especially the current indications for genetic testing and its clinical management. In 5-10% of gastric cancers there is a familiar pattern. Hereditary cancers, unlike sporadic cancers, are associated with germline mutations in a specific gene. In hereditary diffuse gastric cancer (HDGC), mutations have been identified in specific genes associated with the disease (CDH1 y CTNNA1). The clinical syndrome of HDGC is associated with the appearance at an early age, typically around 40 years, of multiple foci of diffuse gastric cancer (GC), frequently  with signet ring cells and the appearance of lobular type breast cancer. Twenty to fifty percent of patients who meet the clinical criteria for HDGC have a mutation in the CDH1 gene. The presence of a mutation confers a risk of diffuse CG of 67-70% for men and 56-83% for women; and a 42% risk of breast cancer throughout the life of the patient. The main current indications for genetic counseling and study are the presence of 2 or more relatives with CG, one confirmed diffuse, regardless of age; and individuals with CG less than 40 years of age, without previous family history. A multidisciplinary team is key and the main management alternatives are endoscopic follow-up and prophylactic gastrectomy. Just as there has been progress in defining the best clinical management of these patients, this pathology also represents an area of important research interest.