What is Genetic Predisposition? Why Does it Matter?
Macro DNA molecules structure. Credit: Canva.
At its core, cancer is defined as a genetic disease - this means that the genes in a person’s body experience changes that cause cells to grow uncontrollably.
The risk of getting cancer can be influenced by many things. Some factors, like smoking or diet, are things we can control. But other factors, like being exposed to harmful environments, getting older, or having certain genetic mutations passed down in our family, are things we can’t control. Rare cancers make up about 27% of all cancer cases and typically have a much lower 5-year survival rate compared to more common cancers.
While research is still limited, we do know that up to ten percent of rare cancers in the United States may be caused by inherited genetic changes, according to the National Cancer Institute. For certain types of rare cancers, including parathyroid carcinoma, acute myeloid leukemia, and certain childhood cancers, there may be an even higher percentage associated with inherited predisposition. Even a more common cancer can be considered rare if it is related to certain genetic predispositions, most of which are themselves rare.
In the Q&A below, we spoke with Catherine Skefos, M.A., M.S., a certified genetic counselor who works with the Clinical Cancer Genetics Program at MD Anderson Cancer Center in Houston, Texas.
Headshot of Catherine. Credit: MD Anderson.
She discusses what genetic predisposition is and explains how understanding genetic risk factors can help people learn more about their health, especially if they have a family history of rare cancers.
Q: What is a genetic/hereditary predisposition to cancer?
A: We all are born with over 20,000 genes in every cell of our body, and these genes provide the instruction manuals for how our bodies grow and develop. So we have a set of genes related specifically to cancer risk. These genes are actually meant to protect our bodies from developing cancer, so if someone is born with a change or a mutation in one of those genes, it leads to the body not being able to fight off cancer like it's supposed to. That's what leads to the increased risk of cancer with hereditary predispositions. So really, when we think about genetic risk or hereditary risk for cancer, we're thinking about the question of this person's risk compared to the general population.
Q: What does a genetic counselor do?
A: Not every patient meets with a genetic counselor, but in an ideal world, I think that every patient would meet with a genetic counselor before having genetic testing done. For those patients that we do meet with, we often will meet with them before testing is done to do a really thorough evaluation of their family history and medical history to determine whether any genetic testing need is indicated. From there, we will coordinate the genetic testing. Then, once results come back, we will interpret those results for the patient, helping them to understand the meaning of the results.
If testing comes back totally normal, we might help them understand their cancer risk based on their family history. If the results come back positive, we can help them understand what that means in terms of future cancer risk, as well as what that means for their family members, and help them to sort of adjust to that risk or come to terms with that new knowledge about themselves. That's often where the counseling part comes in, because it can be difficult sometimes for people who get a positive genetic test result to work through things like family dynamics. How do I communicate this with my children? How do I communicate this information with a relative who might be estranged? Genetic counselors can really help patients work through these topics.
Q: How do I know if I have a genetic predisposition for cancer?
A: What we would want to do is genetic testing on healthy tissue, and it's important to distinguish between genetic testing done on cancer tissue, which is called somatic testing, versus genetic testing done on healthy tissue.
The genetic testing done on healthy tissue is what can help us to know whether there's a hereditary or inherited predisposition. So we would do that genetic testing either on a saliva sample or a blood sample. For people who have active blood cancers, or in people who have had a stem cell transplant from a donor, we would need to do the genetic testing on a skin punch biopsy to represent healthy tissue that a person was born with.
Q: Are there any preventive measures a person can take based on their genetic risk results?
A: So the whole idea behind genetic testing is not just to know about the risk, but then to be able to do something about the risk. And so when we think about preventative measures, sometimes that can look like risk-reducing surgeries, such as prophylactic mastectomies for high breast cancer risk. Of course, all of that would be done in coordination with high-risk oncologists or surgeons that can help to help a person further understand their risk and the risks and benefits of surgery.
Oftentimes, too, what we're thinking about is not just risk reduction and prevention, but also thinking about early detection, which is a huge benefit of genetic testing. It will allow us to really customize a person's screening recommendations so that perhaps they're having screening done that would not be done in a general population setting, or we may recommend having those screenings that other people have, like mammograms or colonoscopies, but perhaps starting them at an earlier age or doing them more often with the goal of early detection.
Q: How is genetic information protected and kept confidential? Are there any other concerns that could be raised from genetic testing?
A: I think one thing is making sure that the genetic testing lab that is being used is covered by HIPAA privacy laws. Genetic testing labs should always be willing to provide information about their privacy policies as well, so that's something that people can look into when choosing genetic testing for themselves. If genetic testing is ordered in a clinical setting, the lab results become part of the patient’s medical record, and so they are then protected under the same policies and regulations that a hospital would use to protect their other health data.
I also do want to mention that sometimes people along the same lines are worried about genetic discrimination and whether genetic testing can be used against them in any way. There's a federal law called the Genetic Information Non Discrimination Act (GINA) that protects health insurance and most employment from discrimination when it comes to genetic test results. That means, for example, a patient's health insurance company is not allowed to use genetic information to increase their rates or drop them from coverage. There are some limitations to the law, though, for instance, it does not apply to new policies taken out for things like life insurance, long term care insurance or disability insurance.
Q: Why is this information so important, especially for rare cancer patients?
A: I think that for patients with certain rare cancers, there can be a large hereditary component. It's a great question for a person with rare cancer to ask their team regarding whether genetic testing is indicated when it comes to their particular diagnosis. But I think that overall, we're learning more and more about hereditary predisposition, and even if something is found on genetic testing that may not be related to the original diagnosis, it can be really useful for a patient and for their family members in helping to understand risk moving forward. I think for many people, genetic testing results can bring up a lot of complex feelings and reactions. But ultimately, I think patients feel that genetic testing is a way to really learn about themselves, learn about their family, and to be able to pass along that information that can be really powerful for them. I think that genetic testing can also help people feel more in control of their care and more in control of the future, if they do, sort of gain that window into potential future cancer risks.
Sometimes, patients need to be their own advocates. If this is something that they're interested in, they should not hesitate to ask their doctors. Many labs these days offer genetic testing for relatively affordable prices out-of-pocket, and so I always encourage people to at least have the conversation. If you have the conversation with a genetic counselor or with your provider and you ultimately decide not to have genetic testing, that's totally fine, but at least have the conversation if it's something that you're interested in.
Our guidelines for who should have genetic testing don't always encompass all rare cancers, and so I think it's also important for patients with rare cancers to just ask that question of whether or not it is something to pursue.
