Unique challenges of risk-reducing surgery for hereditary diffuse gastric cancer syndrome: a narrative review

Abstract

The common use of genetic testing has reinvigorated discussions surrounding enhanced cancer surveillance, chemoprevention, and preventive surgery strategies due to increasing recognition of pathogenic germline genetic variants. Prophylactic surgery for hereditary cancer syndromes can significantly reduce the risk of developing cancer. Hereditary diffuse gastric cancer (HDGC), characterized by high penetrance and an autosomal dominant inheritance pattern, is causally linked to germline mutations in the CDH1tumor suppressor gene. Risk-reducing total gastrectomy is currently recommended in patients with pathogenic and likely pathogenic CDH1 variants; however, the physical and psychosocial sequelae of complete stomach removal are substantial and need to be investigated further. In this review, we address the risks and benefits of prophylactic total gastrectomy for HDGC in the context of prophylactic surgery for other highly penetrant cancer syndromes.