Hereditary Stomach Cancer: When Prevention Becomes the Best Treatment
Most stomach cancers occur sporadically, but around 2% of cases are hereditary. The most common cause is a mutation in the CDH1 gene, which is associated with a condition known as Hereditary Diffuse Gastric Cancer (HDGC).
Individuals who carry a CDH1 mutation have a significantly increased risk of developing stomach cancer, with the lifetime risk estimated to be between 60% and 80%. Women who inherit this mutation also have an increased risk of developing lobular carcinoma of the breast.
Why Is This Cancer Different?
Hereditary diffuse gastric cancer often develops at a younger age, frequently before the age of 50. Unlike the more common intestinal type of stomach cancer, diffuse gastric cancer grows by spreading within the wall of the stomach rather than forming a distinct mass.
This growth pattern creates two major challenges:
- Early detection is difficult. Even a high-quality gastroscopy may fail to identify early cancer because the disease can be hidden beneath a normal-looking stomach lining.
- Symptoms are often absent. Many patients develop few or no symptoms until the disease has reached an advanced stage.
Who Should Consider Genetic Testing?
Genetic counselling and testing should be considered for:
- Families of individuals with a history of diffuse gastric cancer, regardless of the age at diagnosis.
- Families with Individuals diagnosed with stomach cancer at a young age, particularly before the age of 40.
- Families of Individuals with a history of lobular breast cancer.
Identifying a CDH1 mutation can be life-saving, as it allows preventive measures to be considered before cancer develops
Treatment and Prevention Options
1. Endoscopic Surveillance
Patients may undergo regular surveillance with:
- Gastroscopy
- Endoscopic ultrasound
- Multiple biopsies taken throughout the stomach
These examinations are usually performed every 12 months.
However, surveillance has important limitations. Because diffuse gastric cancer grows within the stomach wall, even repeated endoscopies and biopsies may fail to detect the disease at an early stage.
2. Preventive (Prophylactic) Total Gastrectomy
For individuals with a confirmed CDH1 mutation, the recommended treatment is often prophylactic total gastrectomy—the complete removal of the stomach before cancer develops.
Although this may sound like a major undertaking, modern surgery is usually performed using minimally invasive techniques, making the procedure remarkably safe when carried out in experienced centres.
Most patients adapt well after surgery and are able to lead normal, active, and productive lives.
The operation is generally recommended in early adulthood, often around the age of 20 years, although the timing should be individualized according to the patient’s circumstances and family history.
The Take-Home Message
Hereditary diffuse gastric cancer is uncommon, but its consequences can be devastating if not recognised early. Because conventional surveillance may miss early disease, genetic testing plays a crucial role in identifying individuals at risk.
For those carrying a CDH1 mutation, preventive surgery offers the most effective protection against a cancer that is otherwise difficult to detect and often diagnosed too late.
Understanding your family history and seeking expert genetic counselling can be the first step toward preventing a potentially life-threatening disease.
