CDH1-Related Cancer Risk

The CDH1 gene is classified as a “high penetrance” cancer predisposition gene meaning that pathogenic mutations in this gene are believed to be associated with a significantly increased risk for certain types of cancer.  For example, men and women who have a pathogenic CDH1 gene mutation likely have a 50-70% chance of developing a specific type of gastric (stomach) cancer called diffuse gastric cancer.  Additionally, women who have a pathogenic CDH1 gene mutation have approximately a 42% chance of developing a specific type of breast cancer called lobular breast cancer.


CDH1 cancer screening and risk-reducing options

  • Breast: For women who carry pathogenic CDH1 gene mutations, breast cancer screening with annual mammogram and breast MRI starting at the age of 30 years is typically recommended.  Screening may be recommended earlier for individuals who have a family history of early onset breast cancer.  The option for risk-reducing mastectomy may also be considered.
  • Stomach: At this time, upper endoscopies have not been proven to effectively identify diffuse gastric cancer at early stages. Given the significant risk of diffuse gastric cancer in individuals with pathogenic CDH1gene mutations, a multidisciplinary approach should be taken in the consideration and recommendation for prophylactic total gastrectomy (surgical removal of the stomach).


CDH1 associated therapeutic/ treatment implications

Individuals who have a cancer diagnosis and an identified CDH1 pathogenic mutation should speak with their treating physician about the availability of targeted/ personalized treatment options.

Clinical trials for individuals who have pathogenic mutations in the CDH1 gene might be available now or in the future.


CDH1 genetic testing in other family members

At this point in time, genetic testing in adult family members is generally accepted and recommended.  The appropriate age for genetic testing may be adjusted based on psychosocial and family history factors. It is recommended that family members discuss the risks, benefits and limitations of genetic testing with their physician and/or genetic counselor.  If an adult family member were to test positive for the familial CDH1 gene mutation, the increased cancer screening and risk reducing surgical options discussed above could be considered.  Family members who test negative for a familial CDH1 gene mutation should speak with their medical providers regarding remaining risks for cancer.

Family members who are considering having children should speak with a genetic counselor to discuss risks of passing the familial CDH1 mutation onto offspring before conceiving.  Genetic test results may be used by some individuals for reproductive decision-making including the use of pre-implantation genetic diagnosis (PGD), donor gametes, or adoption.


Future considerations

As research continues to evolve, physicians and researchers will gain a better understanding of how a CDH1 gene mutation will guide medical care.  Because the information provided to patients will almost certainly change, those with a CDH1 gene mutation are encouraged to keep in touch with their medical providers in order to receive updates.




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