Hereditary Mixed Polyposis syndrome and the GREM1 gene

Hereditary Mixed Polyposis syndrome and the GREM1 gene

As the name suggests, Hereditary Mixed Polyposis syndrome results in an increased risk of polyps occurring in the bowel (colon) including adenoma, hyperplastic, hamartoma, juvenile and serrated. These polyps, over time, can become cancerous.

Hereditary Mixed Polyposis syndrome is very rare. It is caused by mutations affecting the GREM1 gene. The best known mutation is a large duplication that occurs in less than 1% of individuals with Ashkenazi heritage.

And yes, in case you were wondering, the gene, GREMLIN1, was named after the movie Gremlins)

What is the cancer risk in Hereditary Mixed Polyposis syndrome

The lifetime risk is not known. However, in a large study comparing Ashkenazi Jewish individuals with and without GREM1 mutations, the colon cancer risk (in the absence of screening) was doubled. That is, there is a moderate risk of colon cancer (10 to 25% lifetime risk compared to the average risk of 6 to 12% lifetime).

Management of Hereditary Mixed Polyposis syndrome

Because it is so rare, specific Australia screening guidelines have not yet been developed.

The key to reducing cancer risk in Hereditary Mixed Polyposis syndrome is to remove the polyps before they become a cancer. Screening usually starts at age 25 or 30 with colonoscopies performed every 3 years or as directed by polyp load.

Does this sound like you or your family? Has a GREM1 mutation been detected in a blood relative? Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer and genetic testing can be organised, if needed. You'll find information on how to make an appointment here

These links may be useful

  • There are no specific support groups for carriers of a GREM1 mutation.
  • The Cancer Genetics section of the Cancer Institute's eviQ website provides up-to-date Australian-based management guidelines. Currently, there are no testing or management guidelines for GREM1.