Background
What are genes?
Genes are a biological material that provide instructions for how our bodies look and function. Genes are found in every cell of our bodies. Genes are made up of a chemical called deoxyribonucleic acid, or DNA.
What are gene variants?
DNA is made up of four building-block chemicals, labeled with the letters A, T, C and G. These letters of DNA need to be in a particular order for genes to work properly. Gene variants, or mutations, occur when the letters are out of order, added or missing.
- Gene variants may or may not affect the function of the gene
- Some gene variants can lead to benign or cancerous tumors
- A gene variant that contributes to the development of a disease is known as a pathogenic or likely pathogenic variant (PLP)
What is genetic testing?
Genetic testing is a type of medical test that looks at the order of the letters in your DNA to determine what gene variants you carry. This may help determine any diseases or disease risks that you have. Genetic testing can look at a specific gene or many genes at once.
What is a genetic counselor?
Genetic counselors have training in medical genetics and counseling to guide patients as they look for more information about how inherited diseases might affect them or their relatives. You can meet with a genetic counselor in person, by phone or by videocall.
A genetic counselor will help guide you through the process of getting a genetic test and interpreting its results. The National Society of Genetic Counselor’s website has a tool for finding a genetic counselor that you can access here.
You may also be able to meet with a doctor, nurse or physician assistant who specializes in cancer genetics, if that resource is available in your hospital or cancer center.
Refer to "Questions to Ask Your Genetic Counseling Provider" for some questions you may want to ask your genetic counselor before having any genetic tests.
Who Would Benefit From Genetic Testing?
There are two main types of gastric cancer: diffuse and intestinal. You may benefit from genetic testing if you have been diagnosed with diffuse gastric cancer (DGC). If you have not had cancer but you have a blood relative (parent, sibling, grandparent, aunt, uncle or cousin) that has been diagnosed with diffuse gastric cancer then you may benefit from genetic testing. Having cases of intestinal gastric cancer and other types of cancers in the family, like breast cancer, can also be a reason to seek genetic testing. If you or a blood relative have been diagnosed with cancer, then it is recommended that you talk to a genetic counselor about whether genetic testing is right for you.
Genetic Testing for Hereditary Gastric Cancer
Diffuse gastric cancer can run in families if there is a pathogenic variant in the CDH1 or CTNNA1 gene. If you or a relative has been diagnosed with diffuse gastric cancer, but no variant has yet been identified in the family, then genetic testing for variants in both the CDH1 and CTNNA1 genes is recommended. If a gene variant associated with diffuse gastric cancer has already been identified in a family member, then, in some cases, an individual can just be tested for that gene to see if they also have the same variant.
The CDH1 gene is found in humans and makes a protein that, when working normally, suppresses the growth of tumors in certain types of tissue, particularly stomach (gastric) and breast tissue. When the CDH1 gene has a pathogenic or likely pathogenic variant, its either fails to make the protein or it makes a protein that fails to function correctly. As a result, tissues are unable to suppress tumor growth that can lead to cancer. The CTNNA gene works similarly.
There are other genes that are known to increase the risk of developing intestinal gastric cancer. These genes are APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and TP53. There is also early evidence to suggest that the genes ATM, BRCA1, BRCA2, CHEK2 and PALB2 may increase the risk of gastric cancer.
If no gene variant associated with gastric cancer has been identified in your family, your genetic counselor may recommend gene panel testing. Gene panel testing involves testing for more than one gene at the same time. Given that there are several genes associated with different forms of gastric cancer, gene panel testing is a common test that may be preferred by patients and health care providers.
All genetic testing is performed on a blood or saliva sample to look for gene variants.
I’ve done genetic testing and have a pathogenic CDH1 variant. Now what?
If you have a PLP variant, you’ll want to consider your screening, surveillance and management options. Information on your options can be found in "What is Hereditary Diffuse Gastric Cancer (HDGC)." In addition, it is important to consider what this means for your family members. Though everyone has two copies of the CDH1 gene, one from their father and one from their mother, it only takes one pathogenic variant in CDH1 for an individual to be at risk for cancer. This type of genetic inheritance is called an autosomal dominant pattern. This pattern means that parents, children and siblings of an individual with a CDH1 variant have a 50 percent chance of having that same variant in their genes.
See "Speaking With Your Family" for some recommendations on how to discuss your genetic testing results with family members. Any relative 18 years old or older is eligible for genetic testing. Anyone considering genetic testing should receive appropriate education and counseling.
Testing children under the age of 18 can be considered based on cancer family history and parents’ preferences; the risks, benefits and limitations of testing children should first be discussed with a genetic counselor.
Reproductive options for individuals with a pathogenic variant in CDH1
If you are considering having children, you may be wondering if there are ways to avoid passing a pathogenic gene variant on to your children. Prior to becoming pregnant, it is recommended to meet with a genetic counselor who specializes in fertility to discuss prenatal diagnoses, the use of a donor or preimplantation genetic testing.
Preimplantation genetic testing (PGT) is a medical procedure that allows people who carry a pathogenic or likely pathogenic gene variant to have children without that variant. The PGT process begins with in vitro fertilization (IVF). Following IVF, when the embryos are about 5-7 days old, a few cells are removed from the outer part of the embryo and the DNA of those cells is checked for the presence of the genetic variant. Only embryos that do not carry the variant are implanted.
It is important to keep in mind that PGT can be an emotional and costly process that requires a commitment of time. Decisions around having children can be complex for individuals and couples. For information and support surrounding these issues, please visit https://sharinghealthygenes.com/
Legal Protections Against Genetic Discrimination
The Genetic Information Nondiscrimination Act (GINA) was signed into federal law in 2008. GINA prohibits health insurers and most employers from discrimination against individuals based on genetic information, including the results of genetic tests and family history information. According to GINA, health insurance companies cannot consider genetic information to be a preexisting condition; nor can they use it to make decisions regarding coverage or rates. GINA also makes it illegal for employers to use genetic information when making decisions about hiring, firing, promoting or other terms of employment. It is important to note that GINA does not apply to the individuals affected with a disease like cancer or those in the military, and it does not offer protections for life insurance, disability insurance and long-term care insurance. More information about GINA can be found by visiting www.ginahelp.org.