Hereditary diffuse gastric cancer: updated clinical practice guidelines.

Area of Science:

• Oncology
• Genetics
• Gastroenterology

Background:

• Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant syndrome linked to CDH1 and CTNNA1 gene mutations.
• It presents with high risks of diffuse gastric and lobular breast cancers.
• Clinical management requires balancing genetic testing accessibility with cancer risk.

Purpose of the Study:

• To present updated clinical practice guidelines for HDGC from the International Gastric Cancer Linkage Consortium (IGCLC).
• To incorporate new evidence on gastric cancer risk variability, surveillance capabilities, and post-gastrectomy management.
• To revise genetic testing criteria and risk management strategies for HDGC.

Main Methods:

• Review of emerging evidence on HDGC risk, surveillance, and surgical outcomes.
• Analysis of international clinical experience and expert consensus.
• Revision of genetic testing criteria and management recommendations.

Main Results:

• Relaxed genetic testing criteria for HDGC, particularly age limits.
• Recognition of variability in gastric cancer risk among HDGC families.
• Increased confidence in endoscopic surveillance as a safe alternative to prophylactic gastrectomy in expert centers.

Conclusions:

• Updated IGCLC guidelines provide a more accessible approach to genetic testing for HDGC.
• Endoscopic surveillance is a viable option for managing gastric cancer risk in selected CDH1 variant carriers.
• Prophylactic total gastrectomy remains the primary recommendation for high-risk individuals, but surveillance offers an alternative for others.