Pathophysiology of Hereditary Diffuse Gastric Cancer

Cate’s Story: Hereditary Diffuse Gastric Cancer

“…A small proportion of all gastric cancers (1%-3%) arise because of a known hereditary syndrome, the most common of which is hereditary diffuse gastric cancer (HDGC) (Pattison & Boussioutas, 2015). This is an autosomal dominant genetic disease characterized by an increased risk of developing diffuse gastric cancer at a young age.…”

“…This is an autosomal dominant genetic disease characterized by an increased risk of developing diffuse gastric cancer at a young age. The gene responsible for HDGC is CDH1, also known as E-cadherin, a germline mutation conferring an 80% risk of developing gastric cancer during the lifetime of the carrier (Black et al, 2014, Pattison & Boussioutas, 2015. Overt gastric cancer frequently appears before 40 years of age but also has been reported in teenage CDH1 carriers (Framp, 2010).…”

“…Overt gastric cancer frequently appears before 40 years of age but also has been reported in teenage CDH1 carriers (Framp, 2010). Females with germline CDH1 mutations face an additional risk of developing lobular breast cancer, with a reported cumulative risk of 60% by the age of 80 years (Pattison & Boussioutas, 2015).…”

“…HDGC is characterized by high disease penetrance, and the management of identified carriers is complicated by the lack of a reliable surveillance method for effective early detection and diagnosis of the multiple signet ring cell carcinomas that are seen with HDGC. Routine endoscopy for known CDH1 mutation carriers has proven to be ineffective in the setting of a cancer that is typically subtle, infiltrating beneath normal mucosa and leaving the stomach to appear normal (Pattison & Boussioutas, 2015).…”

“…CDH1 mutation carriers, such as Cate, should be managed by a team of healthcare professionals (Pattison & Boussioutas, 2015;van der Post et al, 2015 adenocarcinoma and that endoscopic surveillance is not sensitive enough to detect early malignant tumor growth. Having seen her mother and sister die at a young age, she was keen to pursue risk-reduction surgery.…”