Hereditary Diffuse Gastric Cancer: Genetic Insights

Hereditary Diffuse Gastric Cancer (HDGC) is a rare genetic condition characterized by an increased risk of developing diffuse type stomach cancer.

This inherited cancer syndrome is caused by mutations in the CDH1 gene, which plays a crucial role in cell adhesion within the stomach lining.

Individuals with HDGC have a significantly higher lifetime risk of developing stomach cancer, with a particular predilection for diffuse gastric adenocarcinoma.

While HDGC is rare, its impact on health can be severe. Without appropriate intervention, HDGC can lead to significant morbidity and mortality. The essential functions affected by HDGC include digestion, nutrient absorption, and overall gastrointestinal health.

Untreated HDGC poses both short-term risks such as nutritional deficiencies and digestive issues, as well as long-term risks like advanced stomach cancer and its associated complications.

In its early stages, HDGC is often asymptomatic, making it challenging to diagnose. This underscores the importance of early detection through genetic testing and regular screenings for individuals with a family history of stomach cancer.

Early intervention can significantly improve outcomes and reduce the risk of advanced disease progression.

Causes of Hereditary Diffuse Gastric Cancer

Primary Causes:

• CDH1 Gene Mutation: Mutations in the CDH1 gene disrupt cell adhesion in the stomach lining, leading to the uncontrolled growth of cancerous cells over time.
• Family History: Individuals with a family history of HDGC are at an increased risk due to the hereditary nature of the condition.
• Environmental Factors: Exposure to certain environmental factors, such as a diet high in salt and processed foods, can contribute to the development of HDGC.
• Helicobacter pylori Infection: Chronic infection with the bacterium Helicobacter pylori has been linked to an increased risk of gastric cancer, including HDGC.

Secondary Risk Factors

• Smoking: Smoking tobacco increases the risk of developing gastric cancer, including HDGC.
• Obesity: Being overweight or obese is associated with a higher likelihood of developing stomach cancer.
• Alcohol Consumption: Excessive alcohol consumption can contribute to the development of HDGC by irritating the stomach lining.

Symptoms of Hereditary Diffuse Gastric Cancer

Early Symptoms

• Unexplained Weight Loss: Weight loss without a known cause may indicate underlying digestive issues common in early-stage HDGC.
• Persistent Indigestion: Chronic indigestion that does not improve with over-the-counter remedies could be a sign of stomach abnormalities.

Advanced Symptoms

• Abdominal Pain: Severe and persistent abdominal pain may indicate the progression of cancer within the stomach lining.
• Blood in Stool: Presence of blood in stool can be a late sign of advanced HDGC and requires immediate medical attention.

Diagnosis of Hereditary Diffuse Gastric Cancer

• Genetic Testing: Identifying CDH1 gene mutations through genetic testing can confirm a diagnosis of HDGC and guide treatment decisions.
• Endoscopic Biopsy: Biopsy samples obtained during endoscopy can provide crucial information about the presence of cancerous cells in the stomach lining.
• Imaging Studies: Techniques such as CT scans and MRI scans can help visualize the extent of cancer spread within the stomach.
• Endoscopic Ultrasound: This procedure allows for a detailed assessment of the stomach wall layers to determine the stage of HDGC.

Treatment Options for Hereditary Diffuse Gastric Cancer

• Medications: Chemotherapy and targeted therapy drugs are commonly used to treat advanced HDGC by targeting cancer cells and slowing down their growth.
• Dietary Modifications: Following a diet low in processed foods, salt, and alcohol can help reduce the risk of HDGC development and support overall stomach health.
• Physical Activity: Regular exercise can promote healthy digestion, weight management, and overall well-being in individuals with HDGC.