While the overall incidence of stomach cancer in the U.S. has declined steadily over the past 75 years, families with a history of the disease remain at significantly increased risk. Many in these families are turning to genetic testing to find out if they have the genetic mutations that contribute to the cancer, and City of Hope is helping them understand this critical information.

City of Hope hosts one of only eight laboratories worldwide that can screen for the disease. The genetic tests have only been available since late 2006.

City of Hope Molecular Diagnostic Laboratory (Photo by Darrin S. Joy)

Called hereditary diffuse gastric cancer, the inherited version of stomach cancer usually strikes before age 45, and it is linked to a single key gene. Men carrying mutations in this gene bear a 67 percent lifetime risk of the disease; for women, lifetime risk rises to 83 percent.

The gene that puts families at risk is called CDH1. When normal, the gene helps cells cling to one another and form tissues and organs. When mutated, however, the gene presents a serious threat.

“A variety of mutations have been reported, so we must look comprehensively for any changes in the gene,” explained Juan-Sebastian Saldivar, M.D., director of molecular diagnostics in the City of Hope Molecular Diagnostic Laboratory, or CMDL.

The threat of cancer is high enough that a growing number of patients who test positive for mutations are opting for surgery to remove the stomach before the disease gains a foothold, he said.

The CMDL is one of only three laboratories in the U.S. — and just two in California — that offer testing for CDH1 mutations. They also are the only U.S. laboratory testing the gene for large missing sections, called deletions. CDH1 large deletions occur in nearly 7 percent of hereditary diffuse gastric cancer patients who otherwise appear free of mutations in the gene.

Wenqi “Wayne” Zeng, Ph.D., associate director of molecular diagnostics, led development of the test. If clinicians suspect a patient could have CDH1 mutations, “we can screen the entire gene for mutations in the coding region and large deletions, as well,” he said.

The test can be important for women for other reasons, too. “Mutations in CDH1 also are associated with lobular breast cancer,” said Zeng.

Lobular breast cancer is one of two main types of the disease. It develops in the milk-producing glands, while the other main type, ductal, begins in the milk ducts.

CDH1 mutations impart a 39 percent risk for lobular breast cancer.

Patients can request genetic testing through their physicians. The CMDL also offers genetic testing to researchers. The laboratory is certified under the Clinical Laboratory Improvements Amendments of 1988 and is licensed by the state of California. More information is available on the CMDL Web site at www.cityofhope.org/mdl.