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Risk Management for an unaffected person with Lynch Syndrome

These guidelines are recommended for individuals who have not had a Lynch related cancer. Anyone affected with a related cancer should have individualised care based on their own specialist advice.

Exclusion Criteria
Individuals from families who meet criteria for Amsterdam I or II without a mismatch repair defect in their tumour or where molecular tumour or germline testing is possible.

Families with a gastric cancer syndrome.

Individuals and close relatives (parent, sibling or child) with mismatch repair loss in a tumour but no germline mismatch repair gene identified on genetic testing.

Lifetime Risks of Cancer

Cancer MLH1
to 70 yrs
MSH2
to 70 yrs
MSH6
to 70 yrs
PMS2
to 70 yrs
Lynch Syndrome
to 70 yrs
General Population
Risk to 85 yrs
Colorectal
male
34% 47% 22% 20% 38% 10%
Colorectal
female
36% 37% 10% 15% 31% 6.6%
Endometrial 18% 30% 25% 15% 33% 2-3%
Gastric 6% 0.2% 0 6% 1%
Ovarian 8-15% 8-15% Low 9% 1-2%
Urothelial 0.2% 2.2% 0.7% <3% 1%
Small bowel 0.4% 1.1% 0 <3% 0.01%

Risk Management

Colorectal Surveillance

This differs according to the gene mutation. MSH6/PMS2 gene carriers have a lower colorectal cancer risk and there tends to be a later age of onset than in those with a MLH1/MSH2 mutation, unless there is a young onset in the family history.

MSH6/PMS2

  • Annual colonoscopy from 30 years

or

  • 5 years younger than the youngest bowel cancer diagnosis if it was under 35.

These recommendations can be reviewed at 60 years and the frequency reduced if indicated as safe.

MLH1/MSH2

  • Annual colonoscopy from 25 years

or

  • Annual colonoscopy from 5 years younger than the youngest diagnosis of bowel cancer if younger than 30.

These can be reviewed at age 60 years and frequency reduced to 2 yearly if indicated.

Risk reducing medication

Preliminary research has shown that daily aspirin has shown that may reduce bowel cancer risk but the recommended dose has not been established.

Endometrial

Risk reducing surgeries are the only known ways to reduce risk significantly.

Surgical

  • Hysterectomy recommended when childbearing complete or from 40 years.

or

  • Consider 5 years younger than youngest affected with endometrial cancer

Surveillance
This is not recommended as trans vaginal ultrasound scans and biopsy of the endometrium have not been proven as effective. It may be offered as part of a clinical trial.

Ovarian

Risk reducing surgery is the only proven method of reducing cancer risk. Research on high risk groups of women has not shown surveillance to effectively detect ovarian cancer at an early stage.

Surgical

  • Risk reducing removal of the ovaries and fallopian tubes (bilateral salpingo-oopherectomy) at time of hysterectomy

HRT should be recommended until usual time of menopause.

Surveillance

  • This is not recommended as trans vaginal ultra sound and CA125 blood measurement has not been proven to be effective.

Gastric

Although there has not been any research to date that has shown gastroscopy is an effective surveillance method it has been recommended by international gastrointestinal experts for individuals with a high risk of gastric cancer.

Surveillance

  • 2 yearly gastroscopy can be considered from 30 years if:
    • There if a family history of gastric cancer
    • The individual has a high ethnic risk (e.g. Chinese, Japanese)

Urothelial
There is only minimal evidence of benefit from surveillance by urine cytology. Therefore prompt reporting any symptoms to the family doctor for specialist review is recommended.

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