In JAMA Oncology Publication, GeneDx Describes Lower Lifetime Risk of Gastric Cancer Conferred by CDH1

Updated Cancer Risk Estimates Will Allow For More Personalized Risk Assessment and Informed Decision Making For Patients with Rare Form of Hereditary Stomach Cancer


GeneDx, Inc., a subsidiary of BioReference Laboratories, Inc.,  and a recognized leader in genetic and genomic testing, announced the results of a study indicating that the lifetime risk of gastric cancer for individuals with pathogenic variants in CDH1 is significantly lower than previously described. Overall, the lifetime risk of gastric cancer associated with pathogenic CDH1 variants was found to be 42% in males and 33% in females, compared to previously published estimates of 40-70% for males and 56-83% for females. The study, Comparison of CDH1 Penetrance Estimates in Clinically Ascertained Families vs Families Ascertained for Multiple Gastric Cancers was published online in the Journal of the American Medical Association (JAMA) Oncology on June 27, 2019, in collaboration with researchers from the University of Washington.

Germline pathogenic variants in CDH1 cause Hereditary Diffuse Gastric Cancer syndrome and result in increased risk for both diffuse gastric and lobular breast cancers. Previous studies assessing CDH1associated cancer risks were research based and mostly in families with strong histories of gastric cancer, often three or more gastric cancers in the family, which lead to overestimation of gastric cancer risks. In this study, GeneDx and the University of Washington estimated CDH1-associated cancer risks based on a group of patients that were not selected based on strong family histories of gastric cancer. While those families reporting three or more gastric cancers had a higher risk for gastric cancer (64% for men and 47% for women), the risk dropped dramatically in families reporting two or fewer gastric cancers (27% for men and 24% for women).

“The estimates derived in the JAMA Oncology paper suggest that lifetime gastric cancer risk is lower than previously reported, albeit still substantially elevated for such an overall deadly cancer,” says Jeremy Davis, surgeon-scientist in the National Cancer Institute’s Center for Cancer Research. Davis leads the largest prospective study of CDH1 mutation carriers in the United States.  “I plan to share this data with participants in my study,” said Davis.

“Patients and clinicians have been making the decision to undergo prophylactic gastrectomy based on outdated gastric cancer risk estimates, and this data suggests that this procedure may not be needed for all individuals with a pathogenic variant in CDH1,” said Benjamin D. Solomon, M.D., FACMG Managing Director of GeneDx. “The findings from this study will allow for more personalized cancer risk assessment, allowing for more informed medical management decisions.”

The study consisted of a retrospective query of over 109,000 individuals who had germline testing of CDH1 completed at GeneDx between August 2013 and June 2018. CDH1 pathogenic variants were identified in 238 individuals from 75 families identified through clinical ascertainment and multigene panel testing. Cancer status was available for 1,679 relatives. Penetrance estimates were based on 41 families for which complete pedigrees were available.

About GeneDx, Inc.
GeneDx, Inc. is a global leader in genomics, providing testing to patients and their families from more than 55 countries. Led by its world-renowned whole exome sequencing program, GeneDx has an acknowledged expertise in rare and ultra-rare genetic disorders, as well as one of the broadest menus of sequencing services available among commercial laboratories. GeneDx offers a suite of additional genetic testing services, including diagnostic testing for hereditary cancers, cardiac, mitochondrial, neurological disorders, prenatal diagnostics and targeted variant testing. GeneDx is a subsidiary of BioReference Laboratories, Inc., a wholly owned subsidiary of OPKO Health, Inc. To learn more, please visit

About BioReference Laboratories, Inc.
BioReference Laboratories, Inc. provides comprehensive testing to physicians, clinics, hospitals, employers, government units, correctional institutions and medical groups. The company is in network with the five largest health plans in the United States, operates a network of 10 laboratory locations, and is backed by a medical staff of more than 160 MD, PhD and other professional level clinicians and scientists. With a leading position in the areas of genetics, women’s health, maternal fetal medicine, oncology and urology, BioReference and its specialty divisions, GenPath and GeneDx, are advancing the course of modern medicine. For more information, visit

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