20 Jun Lifetime Cancer Risk with Germline CDH1 Variants

MedicalResearch.com Interview with:

Dr. Davis

Dr. Jeremy L. Davis M.D.
Surgical Oncologist
Center for Cancer Research
Dr. Davis’ research focuses on sporadic and inherited forms of stomach cancer.
National Cancer Institute

MedicalResearch.com: What is the background for this study?

Response: Individuals who are born with a CDH1 gene mutation are at increased risk of developing specific cancers in their lifetime. Those cancers are called diffuse-type gastric cancer and lobular breast cancer.

The background that is relevant here is that when mutations in this gene were first identified as the cause of inherited forms of these cancers, the estimated lifetime risk of gastric cancer, for instance, was around 60-83%. Because of this very high risk and because gastric cancer is particularly difficult to treat, many experts recommend prophylactic surgery to remove the stomach. In recent years, as we have seen more families who carry a CDH1 gene mutation, we have also observed that gastric cancer rates did not seem quite as high as those risk estimates would have suggested. We sought to re-evaluate lifetime risk of cancer with a large and diverse cohort of individuals throughout North America.

MedicalResearch.com: What are the main findings?

Response:  The main findings are that lifetime risk of diffuse-type gastric cancer in families with CDH1 mutations is much lower than previously described, especially in those with no known family members affected by gastric cancer. And, when we factor in a family’s history of gastric cancer, we can provide some level of risk-stratification based on this additional information.

MedicalResearch.com: Who should be tested for these variants?

Response:  There are well-established guidelines published by an international consortium of experts, last published in 2020 in Lancet Oncology by Blair et al. These guidelines for genetic testing include important parameters, such as a family history of diffuse-type gastric cancer, lobular breast cancer, or both. We would suggest that all individuals meet with a certified genetic counselor before any germline genetic testing.

MedicalResearch.com: What should readers take away from your report?

Response: This study shows that even though individuals with germline CDH1 gene mutations have a higher risk of developing diffuse-type gastric cancer and lobular breast cancer that the general population, this risk is not quite as high as we once thought. Therefore, individuals and their physicians should take this into account when considering risk-reducing strategies such as enhanced cancer surveillance and prophylactic surgery.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: Although this is the first study to provide some form of risk-stratification for individual patients and families, we still need more precise estimates of risk so that we, as clinicians, can appropriately inform patients and families. There are likely other factors that contribute to risk that have yet to be determined, and that is where our future research is focused.

MedicalResearch.com: Is there anything else you would like to add?

Response: Individuals who are identified with germline CDH1 mutations that predispose to cancer should be referred to centers with expertise, as this is a rare condition.

Citation: Ryan CE, Fasaye G, Gallanis AF, et al. Germline CDH1 Variants and Lifetime Cancer Risk. JAMA. Published online June 14, 2024. doi:10.1001/jama.2024.10852

https://jamanetwork.com/journals/jama/fullarticle/2820241

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Last Updated on June 20, 2024 by Marie Benz MD FAAD