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Facts for people and families with Polymerase proofreading-associated polyposis (PPAP)

This fact sheet contains general information about polymerase proofreading-associated polyposis (PPAP).  Each person should be referred to a genetic service for further information and advice. 

Key Points

  • People with a faulty POLE or POLD1 gene have PPAP.
  • Both men and women with a faulty POLE or POLD1 gene have an increased chance of developing polyps in the bowel and small intestine (duodenum).
  • Polyps are not cancerous but if left untreated, bowel (colorectal) or duodenal cancer can develop.
  • Both men and women with a faulty POLE or POLD1 gene have an increased chance of developing brain cancer.
  • Women with a faulty POLE or POLD1 gene have an increased chance of developing endometrial (uterine) cancer.
  • Men and women can be referred to a genetic service where experts can provide information, advice and support about their chance of developing cancer and the option of genetic testing. 
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POLE and POLD1 are ‘DNA repair’ genes that help to protect against bowel and small intestine polyps. They also help to protect against bowel, small intestine, endometrial and brain cancer. 

Everyone has two POLE genes and two POLD1 genes (one from their mother, and one from their father). If one of these genes is not working, this is known as having a faulty POLE or POLD1 gene, or having a POLE or POLD1 mutation. People with a faulty POLE or POLD1 gene are known to have polymerase proofreading-associated polyposis.

Faults in the POLE and POLD1 genes have only recently been discovered and the chance of developing cancer is not yet known. It is estimated that:

  • Both men and women with a faulty POLE or POLD1 gene have an increased chance of developing polyps in the bowel and small intestine over their lifetime.
  • Both men and women with a faulty POLE or POLD1 gene have an increased chance of developing bowel, small intestine and brain cancer over their lifetime
  • Women with a faulty POLE or POLD1 gene have an increased chance of developing endometrial cancer over their lifetime.
  • Not everyone who has a faulty POLE gene or a faulty POLD1 gene will develop cancer.

Cancer in men and women:

  • To find bowel polyps and bowel cancer early, people with a faulty POLE or POLD1 gene should have bowel cancer screening every 2 years from age 25 years. This involves having a colonoscopy. If polyps are found on colonoscopy, bowel screening may be performed more frequently.
  • To reduce the chance of getting bowel cancer, people with a faulty POLE or POLD1 gene may be advised to have surgery to remove the bowel (colectomy) if they are found to have bowel polyps that cannot be removed at colonoscopy.
  • To reduce the chance of getting bowel cancer, doctors may recommend taking daily aspirin.
  • To find polyps and small intestine cancer early, people with a faulty POLE or POLD1 gene should have their duodenum screened every 5 years from age 25 years. This involves having a gastroscopy.
  • There is no reliable method of screening for brain cancer. People with a faulty POLE or POLD1 gene should see a doctor immediately if they develop any worrying symptoms.

Cancer in women:

  • There is no reliable method of screening for endometrial cancer.
  • To reduce the chance of getting endometrial cancer, women with a faulty POLE or POLD1 gene may consider having their uterus removed (risk-reducing hysterectomy) from age 40 years. 

Adult family members of someone with a faulty POLE or POLD1 gene can have genetic testing to check who has the faulty gene and who does not. Their doctor can refer them to a genetic service to find out more about their chance of developing cancer and what genetic testing involves.

If a person does have a faulty POLE or a POLD1 gene:  

  • they can pass it on to their children
  • each child has a 50% (1 in 2) chance of being born with it. Pregnancy planning options are available to people who want to prevent the faulty gene from being passed on.

If a person does not have a faulty POLE or POLD1 gene:

  • they have the same chance of developing cancer as the general population (unless there are other factors that increase this risk)
  • they cannot pass it on to their children.

People who decide not to have genetic testing should still get advice about managing their chance of developing cancer.

Version 3

Date Summary of changes
07/03/2022

Consumer information sheet reviewed in line with risk management protocol (ID 1913). Approved for publication with the following changes made:

  • Title: added 'Polymerase proofreading-associated polyposis'
  • Key points: added 'Both men and women with a faulty POLE or POLD1 gene have an increased chance of developing brain cancer.'
  • What is a faulty POLE or POLD1 gene?
    • First sentence: added 'bowel and small intestine polyps'
    • Second sentence changed to 'They also help to protect against bowel small intestine, endometrial and brain cancer'
  • What is the risk of cancer for people with a faulty POLE or POLD1 gene?
    • Added: 'Both men and women with a faulty POLE or POLD1 gene have an increased chance of developing polyps in the bowel and small intestine over their lifetime.'
    • Bullet 2: brain cancer added
  • How can this increased risk of cancer be managed?
    • Cancer in men and women:
      • Bullet 1: added 'bowel polyps'. Colonoscopy screening changed from 'every 3 years' to 'every 2 years'
      • Bullet 4: 'To find polyps in the duodenum' changed to 'To find polyps and small intestine cancer early'
      • Bullet 5: added 'There is no reliable method of screening for brain cancer. People with a faulty POLE or POLD1 gene should see a doctor immediately if they develop any worrying symptoms'
    • Cancer in women:
      • Bullet 2: 'As the risk of uterine cancer is not well known, removal of the uterus (hysterectomy) is not recommended for women with a faulty POLE or POLD1 gene.' changed to 'To reduce the chance of getting endometrial cancer women with a faulty POLE or POLD1 gene may consider having their uterus removed (risk-reducing hysterectomy) from age 40 years.'

Version increased to V.3. To be reviewed again alongside protocol ID 1913 when next due for review.

Version 2

Date Summary of changes
30/05/2019

Document reviewed in line with protocol ID 1913 following November 2018 CG reference committee meeting. Approved for publication with the following changes made:

Key points section:

  • Specific mention of mutations (p.L424V) and (p.S479N) removed.
  • 'POLE or' added to fourth bullet point.

What is the risk of cancer for people with a faulty POLE or POLD1 gene? section:

  • 'POLE or' added to second bullet point.

How can this increased risk of cancer be managed? section:

  • Bowel cancer and duodenal polyp screening recommendations updated.
  • Sentence added: 'To reduce the chance of getting bowel cancer, doctors may recommend taking daily aspirin.'
  • 'with a faulty POLD1 gene' removed from the sentence 'Cancer in women with a faulty POLD1 gene'.
  • 'POLE or' added to sentence on not recommending hysterectomy.

Version updated to V.2. To be reviewed again alongside protocol ID 1913 when next due for review.

Version 1

Date Summary of changes
27/04/2018 Developed in conjunction with consumer information sheet working group and presented at the November 2017 Cancer Genetics meeting. Discussions continued over email and document approved for publication as V.1. 

This cancer genetics fact sheet is a guide only and cannot cover every possible situation. The information provided is not intended to replace discussion with a health professional, and should not be interpreted as medical advice. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use of this document is subject to eviQ's disclaimer available at www.eviQ.org.au/copyright  

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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/3434

11 Oct 2024