Hereditary Diffuse Gastric Cancer

Stomach tumors can have a genetic basis and hereditary diffuse gastric cancer (HDGC) represents approximately 1-3% of all gastric tumors.

It is associated with a very specific gene mutation that can run in some families called the CDH1 or Cadherin 1 gene. Genes determine are characteristics, out “make-up” as well as certain illnesses we can suffer.

Cadherin is a protein found on cell walls, including those of the stomach. They are the binding proteins that keep your cells together.

When the mutation occurs, there is an 80% lifetime chance of developing the disease.

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Are Stomach Tumors Hereditary?

Yes, hereditary diffuse gastric cancer is inherited as an autosomal dominant condition. 

When you are conceived, you receive one gene from your mother and one from your father.

To get the CDH1 gene mutation, either your mother or father needs to be a carrier of the mutation which is then passed on to you.

There is a 50:50 chance of having the abnormal gene if one of your parents has it.

Diagram Showing HDGC Inheritance

CDH1 Inheritance Of Hereditary Diffuse Stomach Cancer

Hereditary Diffuse Gastric Cancer Diagnosis

There’s  a set of criteria set out by the International Gastric Linkage Consortium (1). These are:

Two or more first or second degree relatives (parents, siblings, aunts, uncles, nieces, nephews) with confirmed diffuse hereditary stomach malignancy, signet ring cell type with at least one diagnosed before the age of 50 years

Three or more confirmed cases of diffuse disease amongst first or second degree relatives (parents, siblings, aunts, uncles, nieces, nephews) independent of age

Hereditary diffuse gastric cancer in two relatives with confirmed HDGC with it confirmed in 1 relative (parents, siblings)

Diffuse disease in anyone under the age of 40 years, regardless of family history

Those with a family history of signet ring cell tumors with one case less than 50 years of age and lobular breast malignancy.

Is HDGC Associated With Other Diseases?

If you are female and carry the CDH1 gene, you have a 39-50% risk of developing lobular breast tumors (2).

If you have a relative with HDGC and are female, you should be referred for screening before the age of 40 years.

There have been reports of other malignancies including bowel, pancreas, lung, prostate and salivary gland tumors.

How Is The CDH1 Gene Defect Diagnosed?

The CDH1 gene defect in hereditary stomach malignancy is diagnosed via a simple blood test. This is then sent to the lab where it is analysed by a process known as PCR or polymerase chain reaction and gene sequencing.

Screening Of CDH1 Positive Individuals

Knowing you have the CDH1 gene represents a difficult dilemma. Knowing that you have such an increased risk really leaves you with 2 options.

The first is regular endoscopic assessments every 6 to 12 months with multiple tissue biopsies taken during the test or to have a prophylactic gastrectomy with all the inherent risks and complications.

Also, you have to remember that hereditary diffuse gastric cancer is submucosal i.e under the surface of the stomach, so an endoscopy may appear normal on endoscopic assessment and that diagnosis is therefore dependant on the depth and accuracy of taking a biopsy.

Genetic Screening

If you have a family history of HDGC you should be referred by your doctor to a genetic councillor.

They can confirm whether you have the cadherin gene abnormality and discuss the best way of managing this with you.

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