Introduction
Hereditary diffuse gastric cancer (HDGC) is a rare, inherited form of stomach cancer that is caused by mutations in the CDH1 gene. The condition is characterized by an increased risk of developing diffuse gastric cancer, which can spread throughout the stomach wall and into nearby tissues. HDGC accounts for less than five percent of all stomach cancer cases. Individuals with HDGC have a 70 to 80 percent lifetime risk of developing diffuse gastric cancer, which is much higher than the general population's risk of developing stomach cancer, which is approximately one to two percent. The condition is inherited in an autosomal dominant manner, which means that a person only needs to inherit one copy of the mutated gene from one parent to develop the condition.
What Is the Cause of Hereditary Diffuse Gastric Cancer?
HDGC is caused by mutations in the CDH1 gene. This gene provides instructions for making a protein called E-cadherin, which plays a critical role in the structure and function of cells. E-cadherin helps to hold cells together and maintain the integrity of tissues. Mutations in the CDH1 gene can disrupt the function of E-cadherin, leading to a loss of cell adhesion and increased cell mobility. This can contribute to the development of diffuse gastric cancer, which can spread throughout the stomach wall and into nearby tissues.
What Are the Symptoms of Hereditary Diffuse Gastric Cancer?
The following are the symptoms of hereditary diffuse gastric cancer:
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Abdominal Pain - Individuals with HDGC may experience persistent, dull, or severe abdominal pain or discomfort that may worsen after eating.
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Nausea and Vomiting - Nausea and vomiting are common symptoms of HDGC, which may occur due to the presence of a tumor in the stomach.
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Difficulty Swallowing - HDGC can cause difficulty swallowing (dysphagia), especially when the tumor has grown large enough to obstruct the food pipe.
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Unintended Weight Loss - HDGC can cause unintended weight loss, which may occur due to a reduced appetite, difficulty eating, or malabsorption of nutrients.
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Early Satiety - Individuals with HDGC may feel full even after eating small amounts of food, also known as early satiety.
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Anemia - HDGC can cause anemia due to chronic bleeding in the stomach, which can cause fatigue, weakness, and shortness of breath.
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Gastrointestinal Bleeding - HDGC can cause gastrointestinal bleeding, which can lead to vomiting blood or passing black tarry stools.
How to Diagnose Hereditary Diffuse Gastric Cancer?
Following are the diagnostic methods for hereditary diffuse gastric cancer:
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Genetic Testing - Genetic testing can help identify mutations in the CDH1 gene that are associated with HDGC. A blood or saliva sample is taken from the individual and analyzed in a laboratory to look for changes in the CDH1 gene.
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Endoscopy - Endoscopy involves the insertion of a thin, flexible tube with a camera at the end (endoscope) into the mouth and down the throat to examine the lining of the stomach. During the procedure, a biopsy may be taken to test for the presence of cancerous cells.
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Imaging Tests - Imaging tests such as CT (computed tomography) scans, MRI (magnetic resonance imaging) scans, and PET (positron emission test) scans can help visualize the size, location, and spread of any tumors in the stomach.
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Stomach Biopsy - A stomach biopsy involves the removal of a small piece of tissue from the stomach lining for examination under a microscope to determine if cancerous cells are present.
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Serology - Serology involves testing for antibodies in the blood that are produced in response to cancer cells. Elevated levels of these antibodies may indicate the presence of stomach cancer.
What Is the Treatment of Hereditary Diffuse Gastric Cancer?
The following are the treatment options for hereditary diffuse gastric cancer:
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Surgery - Surgery is the most common treatment for HDGC. The type of surgery will depend on the tumor's size, location, and spread. Partial or total gastrectomy may be performed to remove all or part of the stomach. Lymph nodes in the area may also be removed.
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Chemotherapy - Chemotherapy involves the use of drugs to kill cancer cells. It may be used before surgery (neoadjuvant chemotherapy) to shrink the tumor or after surgery (adjuvant chemotherapy) to kill any remaining cancer cells.
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Radiation Therapy - Radiation therapy involves using high-energy beams to kill cancer cells. It may be combined with chemotherapy before or after surgery to kill any remaining cancer cells.
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Clinical Trials - Clinical trials are research studies that test new treatments or procedures for their effectiveness and safety. Individuals with HDGC may be eligible to participate in clinical trials testing new treatments for the condition.
What Are the Complications of Hereditary Diffuse Gastric Cancer?
Following are the complications of hereditary diffuse gastric cancer:
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Stomach Cancer - The most significant complication of HDGC is the development of stomach cancer. HDGC significantly increases the risk of developing stomach cancer, which can be challenging to treat if not detected early.
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Malnutrition - Surgery to remove part or all of the stomach can lead to malabsorption of nutrients, which can result in malnutrition. This can cause weakness, fatigue, and other health problems.
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Dumping Syndrome - Dumping syndrome is a condition that occurs when food moves too quickly from the stomach to the small intestine. Symptoms include nausea, vomiting, diarrhea, and abdominal pain.
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Weight Loss - Weight loss is a common complication of HDGC, both as a result of the cancer itself and due to the side effects of treatment.
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Nutrient Deficiencies - HDGC can lead to deficiency of certain nutrients, such as iron, calcium, and vitamin B12. This can cause anemia, osteoporosis, and other health problems.
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Psychological and Emotional Effects - Living with HDGC can be stressful and overwhelming, especially for individuals who have lost family members to the disease. Counseling and support groups can help individuals cope with the psychological and emotional effects of HDGC.
What Is the Survival and Prognosis of Hereditary Diffuse Gastric Cancer?
The survival and prognosis for individuals with hereditary diffuse gastric cancer (HDGC) can vary depending on several factors, including the cancer stage, the age at which the cancer is diagnosed, and the effectiveness of the treatment.
Overall, the prognosis for HDGC is generally poor compared to other types of stomach cancer. HDGC tends to be more aggressive and can spread quickly, making it more challenging to treat. According to the National Cancer Institute, the 5-year survival rate for individuals with stomach cancer is approximately 32 percent, while the survival rate for individuals with HDGC is estimated to be lower.
Conclusion:
Hereditary diffuse gastric cancer is a rare genetic condition that significantly increases the risk of developing stomach cancer. It can be difficult to diagnose and treat, and generally have a poor prognosis. However, regular surveillance and early detection can significantly improve the prognosis. Treatment options may include surgery, chemotherapy, and radiation therapy. It is important for individuals with HDGC to work closely with their healthcare team to manage the condition and any potential complications. Counseling and support groups can also help individuals cope with the psychological and emotional effects of HDGC.
