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Hereditary Diffuse Gastric Cancer

An estimated 1 percent to 3 percent of cases of gastric cancers are hereditary diffuse gastric cancer, an inherited cancer syndrome that leads to an increased risk for both diffuse gastric cancer and lobular breast cancer (in women). Patients who inherit the genetic mutation for HDGC are at high risk for developing gastric cancer at a young age.

Diffuse gastric cancer is a specific type of stomach cancer, sometimes also called “signet ring cell cancer” or “linitis plastic.” It tends to affect a large part of the stomach rather than staying in one small area of the stomach. Approximately 20% of all stomach cancers are diffuse gastric cancers, and a small number of these are due to HDGC. The average age for someone to be diagnosed with stomach cancer is 38, although it can be diagnosed much earlier or later than that. Gastric cancers not associated with this syndrome tend to occur in individuals older than 60.

Causes of HDGC

HDGC is an inherited, genetic condition. This means that the cancer risk and other features of HDGC can be passed from generation to generation in a family. The gene most commonly associated with HDGC is called CDH1. A mutation (alteration) in the CDH1 gene gives a person an increased risk of developing gastric cancer and other cancers associated with HDGC. Researchers believe that other genes including CTNNA1 may be associated with HDGC, and studies are ongoing to learn more about these genes.

How is HDGC inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. HDGC follows an autosomal dominant inheritance pattern, in which a mutation happens in only one copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.

Options exist for couples interested in having a child when they know that one of them carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, one cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos that do not have the mutation. PGD has been in use for over two decades, and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

Diagnosing HDGC

Guidelines for the diagnosis of HDGC syndrome have been proposed, but may change over time as more is learned about this condition. Currently, the diagnosis of HDGC is suspected and CDH1 genetic testing should be considered if a person or family meets any of the criteria listed below:

  • Families with 2 or more cases of stomach cancer, with at least 1 being diffuse gastric cancer
  • A person diagnosed with diffuse gastric cancer before age 40
  • Personal or family history of both diffuse gastric cancer and lobular breast cancer, if at least 1 person was diagnosed before age 50
  • Families with 2 or more cases of lobular breast cancer diagnosed before age 50
  • A person diagnosed with multiple different lobular breast cancers before age 50

Genetic testing for mutations in the CDH1 gene is available. However, only about 20% to 30% of families that appear to have HDGC will have a mutation found in the CDH1 gene. Therefore, both clinical and genetic aspects must be considered in counseling individuals about the potential for their family to have HDGC. Talking with a specialist who has training in genetic diseases and conditions, called a genetic counselor or geneticist, who is familiar with the syndrome is recommended.

Information has been sourced from cancer.net, hopkinsmedicine.org and nostomachforcancer.org