Hereditary Diffuse Gastric Cancer: Should You Get Genetic Testing?

Hereditary diffuse gastric cancer (HDGC) is a rare genetic condition associated with an increased risk of developing stomach (or gastric) cancer. In particular, it predisposes you to an aggressive form of gastric cancer known as diffuse-type gastric adenocarcinoma. Also referred to as signet ring cell gastric cancer, gastric linitis plastica or simply diffuse gastric cancer (DGC), this invasive disease has a high likelihood of spreading to other tissues and parts of the body.

Learn more: Causes and Symptoms of HDGC

Gastric cancer is the fifth most common malignancy and a leading cause of cancer-related deaths across the globe. HDGC makes up roughly 1% to 3% of all gastric cancer cases. It is estimated that this inherited syndrome occurs in five to ten per 10,000 births

If you have a family history of DGC and are concerned about your chances of developing gastric cancer, you may wish to consider genetic testing. A genetic test involves analyzing a blood sample and studying your DNA to identify germline mutations associated with HDGC. This includes the infamous CDH1 gene mutation and other rarer mutations known to cause HDGC.

In 2020, the International Gastric Cancer Linkage Consortium (IGCLC) updated their clinical management guidelines for HDGC, which include detailed criteria for genetic testing. This set of guidelines is meant not only for those who might have HDGC, but also people with a history of DGC or lobular breast cancer (LBC) who may want to find out if the relevant genetic mutations run in their bloodlines.

Currently, an HDGC diagnosis is suspected and CDH1 genetic testing should be considered if you or your family meets any of the following individual and family criteria listed below.

Individual criteria

1. DGC below 50 years of age
2. DGC at any age in individuals of Maori ethnicity
3. DGC at any age in an individual who has a personal or family history (first-degree relative) of cleft lip or cleft palate. This is because of reports citing an association between cleft lip/palate and CDH1 gene mutations in families with HDGC.
4. Personal history of DGC and LBC, both diagnosed below 70 years of age
5. Bilateral LBC diagnosed below 70 years of age
6. Gastric in situ signet ring cells or pagetoid spread of signet ring cells in individuals below 50 years of age. These are pre-invasive cancer cells that can be identified through a gastric biopsy.

Family criteria

1. Two or more cases of gastric cancer in a family regardless of age, with at least one confirmed DGC case
2. One or more DGC cases at any age and one or more LBC cases below 70 years of age, in different family members
3. Two or more LBC cases in family members below 50 years of age

Take note that family members must be first-degree (parent, sibling or child) or second-degree (aunt/uncle, grandparent or grandchild) blood relatives of each other.

If you meet the criteria listed above, it’s crucial to consider undergoing genetic testing. It can help in early detection of gastric cancer, which in turn can lead to more effective and timely treatment plans. Making your health a top priority is always essential and can benefit your overall well-being.