Inherited Cancer Risk, Genetic Testing & Gastric Cancer
- Sometimes, a risk for gastric cancer is passed down through families, but this is rare. Hereditary (familial) gastric cancer accounts for 1 to 3% of cases globally.
- Most new gastric cancer cases are sporadic, meaning they are not associated with any underlying disease.
- When it comes to the management of this disease, doctors can look for mutations in two ways: by looking at your DNA for changes or mutations that are present in all cells of your body that you inherited from your parents or that are specific to your tumor cells that were acquired at some point in your lifetime, or at the tumor cells.
- Individuals who have inherited a genetic alteration and are considered high-risk should discuss monitoring with their doctors.
Most new gastric cancer cases are sporadic, meaning they are not associated with any underlying disease. However, a significant set of genetic pathologies has been linked to gastric cancer development. These are called genetic syndromes and they account for 10% of cases, so being aware of and screening for them when appropriate is important.
Read MoreGenetic Testing & Family History
People who have a family history of gastric cancer may be more likely to develop the disease due to an inherited mutation. When it comes to the management of this disease, doctors can look for mutations in two ways: by looking at your DNA or at the tumor cells.“The first category is genetic testing of the patient, of you, and that [checks if] there are any mutations or changes in your DNA that you were born with, whether you were born with it as the first person in the family or [it’s] something you inherited from one of your parents [that affected] all the cells in your body,” Dr. Pintova explains.
“That’s an important aspect of an evaluation of somebody who has either a family history of stomach cancer, has other potential concerns for stomach cancer, or already has a diagnosis of stomach cancer,” she adds.
Knowing your family health history can play a critical role in taking care of your overall health and assessing what diseases you may be prone to in the future. But when it comes to cancer, this information is not always straightforward.
While it can be helpful to speak to relatives, not all patients have access to their family health histories — another reason why genetic testing is important.
Assessing the Characteristics of Your Cancer
The other ways doctors use genetics to assess gastric cancer is by examining the features of cancer that has already developed.
“The other aspect of it is genetic testing … or pathologic features of the stomach cancer itself,” Dr. Pintova explains. “So, not of the patient, not yours, but the genes of the cancer … That is a very important aspect of evaluation and treatment for stomach cancer because we have a number of therapies that work better when the cancer has or doesn’t have certain features. And we also have a number of targeted therapies these days that target specific changes in the DNA of the tumor.”
Truly hereditary (familial) gastric cancer accounts for 1 to 3% of the global burden of gastric cancer. The specific types of gastric cancer linked to family history include:
- Hereditary diffuse gastric cancer (HDGC)
- Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)
- Familial intestinal gastric cancer (FIGC).
The risk of developing gastric cancer is high in these families, but only HDGC has a specific gene mutation associated.
Inherited Syndromes Linked to Gastric Cancer
Gastric cancer has also been associated with several other inherited syndromes, including:
- Lynch syndrome (hereditary nonpolyposis colorectal cancer)
- Familial Adenomatous polyposis
- Li-Fraumeni syndrome
- Peutz-Jeghers syndrome
- Juvenile polyposis
- Hereditary breast and ovarian cancer syndrome
However, it’s rare that these syndromes will lead to the development of gastric cancer.
What is Microsatellite Instability Evaluation?
Thanks to the precision oncology, doctors can now identify the main cell involved in the tumorigenesis — and dive into its nuances. The microsatellite instability investigation is the next step to better define the characteristics of gastric cancer.
“The way to test for that is the pathologist uses certain stains to see if the tumor is expressing or has lost the expression of a number of proteins in the way that they repair DNA,” Dr. Pintova explains.
“Ultimately, if the tumor is microsatellite unstable, that always makes us question whether somebody was born with a genetic syndrome. They may or may not have been, but they should be tested. The second important aspect of the microsatellite instability or stability is that the microsatellite unstable tumors in general respond better to immunotherapy rather than chemotherapy. So it’s important and essential testing of every stomach tumor.”
Others genetics aspects are also important and this is a topic in constant development all over the world.
“There are other markers as well. One that we normally do for metastatic lesions is a test for a protein called HER2. HER2, if it’s overly expressed in the tumor, is very important because we have targeted therapies that target that protein specifically … They work in metastatic disease,” she adds.
Currently targeted or genetic therapies are only used in the setting of metastatic disease.
How Do I Know if I Have a Genetic Syndrome?
Some individuals know they have a higher risk for gastric cancer because parents or other relatives were previously diagnosed.
However, not everyone knows their health history and some individuals who develop gastric cancer are the first in their families to present with the genetic alteration.
If you know or suspect you have a family history of gastric cancer, talk to your healthcare provider about genetic testing.
If you have already been diagnosed with gastric cancer, speak to your doctor about analyzing your tumor for the presence of genetic alterations — and don’t be afraid to ask questions.
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