When a patient who would not normally be recommended for CDH1 genetic testing that is, someone without a family history of gastric cancer undergoes genetic testing with a multigene panel that includes detection of CDH1, the results can be difficult to interpret.

Patients may learn that they carry a pathogenic CDH1variant, which is associated with hereditary diffuse gastric cancer syndrome andalthough the gastric cancer risk is unclear in the absence of a family history,this information may lead to a clinician recommending risk-reducing totalgastrectomy.

Total gastrectomy can lead to long-term morbidity, includinghaving dumping syndrome, weight loss, and nutritional and metaboliccomplications.

Therefore, the discovery of an unexpected CDH1 variant on a multigene panel testin the absence of a family history of gastric cancer can create a difficultconundrum for clinicians and patients, the authors of a commentary publishedin the Journal of the National Cancer Institute explained.1

These challenging situations are being increasinglyencountered in practice, the authors revealed, noting that CDH1 isincluded on many commonly ordered cancer-focused multigene panels.

The concern with unexpected CDH1 variants is there areconsiderable uncertainties regarding CDH1variants and their management. Specifically, the degree of gastric cancer riskassociated with CDH1 variants in patients without a family history ofgastric cancer is uncertain. Furthermore, there is uncertainty about thecancer risk of specific CDH1 variants and limited understanding of thefactors that promote progression of small foci of signet ring cell carcinoma todiffuse gastric cancer in CDH1 carriers.

Despite these uncertainties, excluding CDH1 frommultigene panels may not be a long-term solution because of the increased timeand labor burdens imposed on genetic counselors, the authors of a correspondingeditorial wrote.2

Instead, as the commentary authors propose, patients should beinformed of the uncertainties surrounding CDH1 during pretest counseling,as well as told that if a CDH1 variant is discovered, risk-reducingtotal gastrectomy is the near-global recommendation.

References

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Unexpected CDH1 Variants Lead to Uncertainty, Experts Warn - Cancer Therapy Advisor

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