Updated: What is Diffuse Gastric & Lobular Breast Cancer Syndrome?

Diffuse Gastric and Lobular Breast Cancer Syndrome (DGLBCS)

is caused by a genetic alteration passed down through generations within families. The only causal factors described to date are mutations in the genes CDH1 ( E-cadherin), which occur in up to ~40% of families, and CTNNA1 (alpha-catenin) gene mutations that so far explain ~2% of the families. Both E-cadherin and alpha-catenin are crucial proteins for the establishment of cell-cell adhesion, functioning in the same junctional complex.

Individuals inheriting a single copy of the mutant gene are at increased risk of developing cancer. The particular subtypes of cancer appearing in these families, namely diffuse-type stomach cancer and lobular-type breast cancer, are rare forms of disease, frequently diagnosed at early ages, and difficult to treat successfully.

Those with a confirmed pathogenic variant in CDH1 can consider prophylactic total gastrectomy, though this decision should be made with care and with input from the patient, family, and caregivers. With CTNNA1 gene mutations, the risk for diffuse gastric cancer is less well-defined, and therefore surveillance by annual upper endoscopy as opposed to total gastrectomy is reasonable. Breast cancer surveillance by breast MRI can begin at age 30, though family history may prompt earlier screening.

Every four years, the International Gastric Linkage Consortium (IGCLC) convenes to update the HDGC clinical management guidelines, which provide critical information for medical care providers and for those patients and families at risk. The most recent IGCLC meeting Guidelines Updates occurred in 2024 in Portugal. 

To learn more about Hereditary Diffuse Gastric Cancer, visit No Stomach for Cancer: https://nostomachforcancer.org/

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