Stomach cancer in the U.S. has declined steadily over the past 75 years. Even so, families with a history of the disease remain at increased risk. Many in these families are turning to genetic testing to find out if they have the genetic mutations that can lead to stomach cancer.
Hereditary diffuse gastric cancer, the inherited version of stomach cancer, usually strikes before age 45. It’s linked to a single key gene called CDH1.
In its common, normal form, the gene helps cells cling to one another and form tissues and organs. When mutated, though, the gene presents a serious threat.
Two of every three men with this mutation will develop stomach cancer during their lifetime. For women, lifetime risk rises to 83 percent.
The threat of cancer is high enough that a growing number of patients who test positive for mutations are taking action, opting for surgery to remove the stomach before the disease gains a foothold, according to Juan-Sebastian Saldivar, M.D.
Saldivar is director of molecular diagnostics in the City of Hope Molecular Diagnostic Laboratory, or CMDL, one of just eight laboratories worldwide — and only three in the U.S. — that can screen for mutations in CDH1.
The CMDL also is the only U.S. laboratory testing the gene for large missing sections, called deletions, according to Wenqi “Wayne” Zeng, Ph.D., CMDL associate director of molecular diagnostics. This is important because large deletions in CDH1 are found in nearly 7 percent of hereditary diffuse gastric cancer patients, but no other mutations occur in the gene in these patients. Their genetic risk would go undiscovered through the more common CDH1 genetic test.
The CDH1 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 give rise to a 39 percent lifetime risk for lobular breast cancer.
Curious about genetic testing? Talk about it with your physician to see if it’s appropriate for you. Physicians can request genetic testing for CDH1 or other risk-raising factors through a referral. More information is available on the CMDL Web site.
