Hereditary diffuse gastric cancer
Hereditary diffuse gastric cancer (HDGC) is a rare form of cancer characterized by the simultaneous presence of cancerous cells in multiple areas of the stomach, rather than the formation of localized tumors. This condition is strongly linked to mutations in the CDH1 gene, which is inherited in an autosomal dominant manner, meaning that an individual only needs one mutated copy from a parent to be at risk. While most diagnosed individuals have this mutation, approximately 30% do not, suggesting that other genetic factors may also contribute to the disease. The average age for diagnosis is around 38, with a wide range from 14 to 69 years.
Symptoms often remain absent until the cancer is advanced, leading to issues such as stomach pain, nausea, vomiting, and weight loss. Screening for HDGC is recommended for individuals with a family history, although its effectiveness has not been statistically confirmed. The standard treatment is a complete surgical removal of the stomach, known as gastrectomy. Prognosis heavily depends on the timing of diagnosis; early detection can lead to a five-year survival rate of about 90%, while late-stage diagnosis significantly lowers this rate to below 30%. Due to its hereditary nature, there are currently no known preventive measures for HDGC.
On this Page
Hereditary diffuse gastric cancer
ALSO KNOWN AS: HDGC syndrome
RELATED CONDITIONS: Lobular breast cancer, colon cancer
DEFINITION: Hereditary diffuse gastric cancer is a rare cancer that affects many parts of the stomach simultaneously rather than forming localized tumors.
Risk factors: Hereditary diffuse gastric cancer has a strong inherited component and is highly likely to occur in people who have a mutation on the CDH1 gene. However, other genes are likely involved because 30 percent of people with hereditary diffuse gastric cancer do not have the CDH1 mutation. The average age at diagnosis is thirty-eight (the age range for diagnosis is fourteen to sixty-nine). Among people with a mutated CDH1 gene, the lifetime risk of having the syndrome ranges from 37 to 70 percent in men and 25 to 83 percent in women.
Etiology and the disease process: The CDH1 gene is an autosomal dominant gene, meaning that the individual needs to inherit a mutation in this gene from only one parent to be at risk for hereditary diffuse gastric cancer. Children with one parent with the mutated gene have a 50 percent chance of inheriting the condition. Cancer develops when individual cancer cells invade the stomach wall in many places, causing cancerous patches. This cancer does not form discrete tumors.
Incidence: The rate of all gastric cancers is highest in Asia, but HDGC is more common in the West. Between five and ten births out of 10,000 have HDGC. Hereditary diffuse gastric cancers account for around 2 percent of all gastric cancers.
Symptoms: Most people do not show symptoms until hereditary diffuse gastric cancer is advanced. Advanced cases of the disease cause stomach pain, nausea, vomiting, and bloating, often accompanied by weight loss.
Screening and diagnosis: Although their value in screening remains statistically unproven, endoscopies are recommended for people who have a family history of hereditary diffuse gastric cancer. Colon cancer screening and breast cancer screening are also recommended, as these cancers commonly co-occur in people with hereditary diffuse gastric cancer. Genetic testing for the CDH1 mutation is available, and genetic counseling may be helpful. Diagnosis is most often made on a family history of hereditary diffuse gastric cancer or early gastric cancer and a biopsy.
Treatment and therapy: Because this cancer occurs throughout the stomach, complete surgical removal (gastrectomy) is the standard treatment. TNM (tumor/lymph node/metastasis) staging of hereditary diffuse gastric cancer has not been standardized because of the nature of the cancer and its rarity.
Prognosis, prevention, and outcomes: If diagnosed and treated with early (an uncommon event), the five-year survival rate is about 90 percent. When diagnosed in a late stage (most common), the five-year survival rate is less than 30 percent. Because of its strong inherited component, there is no known way to prevent hereditary diffuse gastric cancer.
Bibliography
Corso, Giovanni, and Franco Roviello. Spotlight on Familial and Hereditary Gastric Cancer. Springer, 2013.
"Hereditary Diffuse Gastric Cancer." National Library of Medicine, www.ncbi.nlm.nih.gov/books/NBK1139. Accessed 30 June 2024.
Nadine Tung, et al. "Selection of Germline Genetic Testing Panels in Patients With Cancer: ASCO Guideline." Journal of Clinical Oncology, 17 May 2024, doi.org/10.1200/JCO.24.00662.
Onitilo, Adedayo A., Govinda Aryal, and Jessica M. Engel. "Hereditary Diffuse Gastric Cancer: A Family Diagnosis and Treatment." Clinical Medicine and Research, vol. 11, no. 1, 2013, pp. 36–41.
"Stomach Cancer Risk Factors." American Cancer Society, 22 Jan. 2021, www.cancer.org/cancer/types/stomach-cancer/causes-risks-prevention/risk-factors.html. Accessed 30 June 2024.