Hereditary Diffuse Gastric Cancer
HDGC is a cancer-associated syndrome characterized by the development of stomach and breast cancer before the age of 50. Of particular importance is the fact that only particular subtypes of stomach and breast cancer appear in HDGC families: diffuse type stomach cancer and lobular type breast cancer. While stomach cancer is the most frequent cancer type in HDGC families, breast cancer is the second most frequent type of cancer in females from these families. Successive generations are often affected by these tumour types and cancer onset is frequent in people in their 20s or 30s.
HDGC is caused by a genetic defect that is inherited within families. There are no other causal factors described to date. CDH1 or E-cadherin gene mutations are the major inherited cause of HDGC and occur in ~40% of families. CTNNA1 or alpha-catenin gene mutations, despite rare, explain ~2% of the families.
HDGC is an autosomal dominant syndrome, meaning that all family generations tend to have affected individuals with either stomach or breast cancer. Individuals inheriting a single copy of the mutant gene are at increased risk to develop cancer. Both men and women carrying the mutant gene have 80% risk of developing gastric cancer by 80 years of age. Women have a further 60% risk of developing lobular breast cancer at the same age. The combined risk to develop any of these cancers in women by the age of 80 is 90%.
Individuals at risk should attend Medical Genetics appointments for genetic counselling and testing. Identified mutation carriers will enter a clinical path where adequate clinical care and follow-up is provided by a multidisciplinary expert team.
The primary disease preventive option is removal of the stomach (total gastrectomy) in people who carry the mutation, despite lacking symptoms of disease. In case gastrectomy is not appropriate, surveillance can be completed with yearly gastroscopy with endoscopy and multiple biopsies.
Yearly mammography and breast MRI from age 35 years onwards is the most adequate screening procedure for early detection of lobular breast cancer. Breast surgery is offered to patients presenting early breast cancer lesions and is generally curative. The preventive removal of both breasts is also an option, but should be carefully discussed with the clinical team.
Endorsed by ERN GENTURIS*
Hereditary diffuse gastric cancer: updated clinical practice guidelines
* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.
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