CDH1 Sequencing and Deletion/Duplication

This test is used to identify individuals with a high risk of developing hereditary diffuse gastric cancer (HDGC) syndrome. The test detects point mutations, deletions, and duplications in the CDH1 gene.

The following individuals may be appropriate for this test:

• Individuals with a personal history of diffuse gastric cancer or lobular breast cancer
• Individuals with a family history of diffuse gastric cancer or lobular breast cancer

Informed consent following genetic counseling is strongly recommended. The person in the family with the earliest diagnosis of stomach and/or breast cancer should be tested first whenever possible.

You can ask one of our genetic counselors. Please call Quest Genomics Client Services at 866.GENE.INFO to talk with a genetic counselor.

Both women and men have a higher risk of stomach cancer, specifically diffuse gastric cancer, than the general population. The lifetime risk of diffuse gastric cancer is up to 83% for women and up to 67% for men.^2,4 Men and women might also have an increased risk of colorectal cancer as compared to the general population. Women have a 39% to 52% lifetime risk of developing breast cancer (lobular carcinoma).^3,4

The right time is different for every patient. A patient’s current medical status, personal experience with cancer, and general readiness for genetic information all influence the decision to be tested. Having an open dialogue with your patient about these topics can assist with shared decision-making.

Patients with a positive result (pathogenic or likely pathogenic variant detected) have an increased risk for developing certain cancers relative to that of the general population.

The National Comprehensive Cancer Network (NCCN) provides up-to-date surveillance and management recommendations (NCCN.org) for patients with a positive result. These include increased surveillance and prophylactic surgery.¹ The NCCN further recommends referring patients to oncology centers experienced in treating patients with a hereditary predisposition to cancer. Counselors and doctors at these centers can discuss available options with patients. Genetic counseling for family members is advised.

A negative result means that a pathogenic or likely pathogenic variant was not detected in the CDH1 gene. Implications of this result depend on the situation:

• Patient previously diagnosed with cancer: Your patient’s risk of recurrence or a related new cancer is based on his/her personal and family histories of cancer. In some instances, it may be appropriate to test for other hereditary forms of cancer. Please call Quest Genomics Client Services at 866.GENE.INFO to discuss possible additional studies with a genetic counselor.
• Patient not previously diagnosed with cancer, but with a family history of cancer: Testing an affected family member is recommended for proper risk assessment. Your patient’s risk of cancer is based on his/her personal and family histories of cancer. In some instances, it may be appropriate to test for other hereditary forms of cancer. Please call Quest Genomics Client Services at 866.GENE.INFO to discuss possible additional studies with a genetic counselor.

A VUS result means that the variant has not been previously described in the literature or that the clinical significance is unclear based upon currently available evidence. Medical management decisions should be based on personal and family history. Family studies may help to learn more about the clinical significance of this variant. If you have questions, please call Quest Genomics Client Services at 866.GENE.INFO to speak with a genetic counselor.