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Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer



Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer Syndrome - HDGC

Gastric cancer refers to cancer of the stomach.  Gastric cancer is a fairly common cancer worldwide, seen more commonly in Latin and Asian countries such as Japan, and more rarely in North America, with Ontario having one of the lowest incidences in the world. 

It occurs more commonly in men than women, and has been associated with various risk factors including diets high in pickled, cured, salted, smoked food and lower in fruits and vegetables;  smoking; alcohol consumption; a blood condition known as pernicious anemia; and other environmental factors (e.g. asbestos).  It has also been strongly associated with infections caused by Helicobacter pylori (H. pylori) bacteria.  
H. pylori is a bacteria that is found in the stomach and intestinal tract and is often silent, causing no symptoms.  However, if left untreated, it can cause ulcers, inflammation of the stomach lining and may lead to gastric cancer.  If H. pylori is detected through screening, it can be treated using antibiotics.

Hereditary Diffuse Gastric Cancer

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What is diffuse gastric cancer?

There are different types of tumours that can arise in the stomach.  Most gastric cancers arise from the cells of the stomach lining, and are called adenocarcinomas.   Adenocarcinomas can be further divided into intestinal-type or diffuse-type tumours based on the histology or the look of the tumour.
A pathologist would be able to determine whether the cancer is the diffuse-type, and some words that might be used by the pathologist include “signet ring carcinoma”, “diffusely infiltrating”, “poorly differentiated”, “mixed or isolated cell types”.   “Linitis plastica” is an older term that describes diffuse-type gastric cancer.
 

What is HDGC?

Hereditary Diffuse Gastric Cancer or HDGC is an inherited form of gastric cancer caused by a mutation in the E-cadherin/CDH1 gene located on chromosome 16.   We each have two copies of the E-cadherin/CDH1 gene, one we inherit from our mother and the other we inherit from our father.   If a person is born with a problem or a mutation in this gene (from either mother or father), he/she will have HDGC and be at a much higher risk to develop diffuse-type gastric cancer. 
It has been estimated that the lifetime risk to develop gastric cancer in patients with HDGC is around 70%.  The average age of onset in both men and women is 38 years old, although it has been seen at younger ages in some individuals with HDGC.

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Who is eligible for genetic testing for HDGC?

Eligible families who have at least two relatives with diffuse-type gastric cancer, at least one diagnosed under age 50, or families with at least three relatives with diffuse-type gastric cancer at any age.  Families with once case of very young diffuse-type gastric cancer (e.g. under age 35), or families with diffuse-type gastric cancer and lobular breast cancer may also be considered.
Testing requires a blood sample from a family member who has diffuse gastric cancer, and we may also ask permission to obtain medical records to confirm the cancer and access to the tumour sample stored at the hospital. 
Of families meeting the criteria above, less than half (~40%) will have a mutation identified in the E-cadherin/CDH1gene.  If a mutation is identified in a family, genetic counselling and testing would be offered to affected and unaffected family members.  The chance that a parent passes down HDGC is 50%, therefore there would be a 50% chance that a child did NOT inherit the mutation.  Treatment for HDGC is discussed below.
For patients with diffuse gastric cancer that did not have an E-cadherin mutation identified, research will continue looking for the genetic cause of gastric cancer.  

If your family has a young onset of intestinal-type gastric cancer, or a family history of intestinal-type gastric cancer with colorectal cancer and polyps, you may be eligible for genetic testing for other types of inherited cancer syndromes.


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What is the treatment for HDGC?

Unfortunately, HDGC cannot be cured, and due to the aggressive nature of gastric cancer, there are no effective screening tools to detect it at an early stage.  For patients with confirmed E-cadherin/CDH1 gene mutations, surgery to remove the stomach is recommended. 
Colonoscopy and mammography would also be recommended.
If a families is not found to have a genetic mutation, screening recommendations would be considered on an individual basis based on the suspicion of HDGC in the family.   These may include upper endoscopy screening where a flexible scope is passed through the mouth into the stomach, and special dyes and/or random biopsies may be used to monitor the stomach lining.

 

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Hereditary Diffuse Gastric Cancer

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