Risk Management for CDH1 Mutation Carrier
Hereditary diffuse gastric cancer is frequently associated with a germline mutation in the CDH1. This is inherited in an autosomal dominant pattern.
This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer/tumour.
Management guidelines are based on the data generated from high-penetrant HDGC families and may not reflect the risk for individuals with a CDH1 mutation without a personal or family history of diffuse gastric cancer or lobular breast cancer.
Cancer Management Guidelines
Individualised screening may be required if there has been a breast cancer diagnosed 35 years and younger.
- Start at 30 years
- Annual MRI’s and mamograms (with or without Ultra sound scans as determined by the specialist) between 30 and 50 years
- Annual mammograms (with or without ultra sounds) 50 years and onwards
Contraindications: Pregnancy but ultra sound scans can be considered
Risk Reducing Medication
There is limited evidence but risk reducing medication should be considered on a case by case basis
Risk Reducing Surgery
The option of risk-reducing mastectomy should be discussed
- There are no reliable screening tests to allow early diagnosis.
- The gastric cancers are signet cell cancers which develop beneath an intact surface epithelium. Visibility on direct mucosal evaluation occurs late in the disease process
- Endoscopic surveillance may be considered
- Mutation carriers identified prior to 20y may be recommended to undergo annual surveillance endoscopy with surgery deferred until after 20y
- Patients >20y who receive a recommendation for prophylactic gastrectomy, but who decide to postpone (or refuse) the procedure due to young age, fertility concerns, or fear of surgery with associated complications
- Individuals with mutations of uncertain significance and in those in whom a mutation cannot be identified in the index case
Risk Reducing Surgery
- Prophylactic total gastrectomy is recommended for any individual with an appropriate pedigree who has been shown to have a germline CDH1 mutation
- Prophylactic gastrectomy recommended between 20-30y (mean age of onset 38y). Some kindreds have a much younger age of onset, which may influence timing of surgery. Some recommended consideration of gastrectomy 5y younger than youngest affected family member.
- In affected kindreds with a family history of colorectal cancer
- Surveillance colonoscopy starting at 40y (or 10y younger than the youngest diagnosis of colon cancer)
- Repeated every 3-5y