What is Hereditary Diffuse Gastric Cancer (HDGC)?
Hereditary Diffuse Gastric Cancer (HDGC) is a rare, inherited cancer syndrome that primarily increases the risk of developing diffuse gastric cancer, a type of stomach cancer that spreads widely throughout the stomach lining. Unlike other forms of gastric cancer, HDGC often does not form a distinct tumor but rather spreads diffusely through the stomach wall.
Genetic Basis of HDGC
HDGC is most commonly associated with mutations in the
CDH1 gene, which provides instructions for making a protein called E-cadherin. This protein helps cells stick together, and mutations can lead to cells becoming less adhesive, which can contribute to cancer growth and spread. Other genes such as CTNNA1 have also been implicated in HDGC, but are far less common.
How is HDGC Diagnosed?
Diagnosis of HDGC often involves a combination of genetic testing, family history evaluation, and clinical features. Individuals with a family history of diffuse gastric cancer or lobular breast cancer may be advised to undergo genetic testing for CDH1 mutations. Endoscopic surveillance and biopsies are also crucial diagnostic tools, given the diffuse nature of the cancer.
Who is at Risk?
Individuals who inherit a pathogenic mutation in the CDH1 gene have a significantly increased lifetime risk of developing diffuse gastric cancer, with estimates ranging from 56% to 70% for men and 30% to 56% for women. Women with this mutation also have an elevated risk of lobular breast cancer, estimated at 39% to 52%.
What Are the Symptoms?
Symptoms of HDGC can be subtle and non-specific, often making early detection challenging. Common symptoms include stomach pain, nausea, vomiting, weight loss, and early satiety. As the disease progresses, these symptoms can become more pronounced.
Preventive Measures and Treatment Options
Given the high risk and difficulty in early detection, prophylactic (preventive) gastrectomy (surgical removal of the stomach) is often recommended for individuals with a confirmed CDH1 mutation. This procedure significantly reduces the risk of developing gastric cancer but comes with its own set of challenges and lifestyle changes. For those who do not opt for surgery, regular endoscopic surveillance is essential.Treatment options for individuals diagnosed with HDGC include surgery, chemotherapy, and targeted therapies, although the diffuse nature of the cancer often makes it less responsive to conventional treatments.
Importance of Genetic Counseling
Genetic counseling is crucial for individuals and families affected by HDGC. A genetic counselor can help interpret test results, assess cancer risk, and discuss appropriate preventive measures. They can also provide emotional support and resources for managing the psychological impact of a cancer diagnosis or the decision to undergo prophylactic surgery.Research and Future Directions
Ongoing research aims to better understand the molecular mechanisms underlying HDGC, develop more effective screening methods, and identify additional genetic mutations associated with the syndrome. Advances in personalized medicine and targeted therapies hold promise for improving outcomes for individuals with HDGC.Conclusion
Hereditary Diffuse Gastric Cancer is a serious and complex condition that requires a multifaceted approach to diagnosis, prevention, and treatment. Genetic testing, counseling, and preventive measures are essential components of managing this inherited cancer syndrome. Ongoing research and advancements in medical science continue to offer hope for better outcomes for those affected by HDGC.
