Ashlee Williams, MD (Host): Many people worry about their risk of cancer, especially if it runs in the family. But how much of our risk is inherited, and when does genetic testing actually make sense? For some people, understanding their unique genetic profile can provide valuable insight and help guide screening, prevention, treatment decisions.

 Welcome to The Healthier You Podcast. I'm Dr. Ashlee Williams. And today, I'm talking with Dr. Pim Suwannarat, a board-certified geneticist at Kaiser Permanente, about how genetic testing can help you better understand your cancer risk. We'll discuss who may benefit from testing, what to expect during genetic testing, and what results can and cannot tell you, and how this can help you make informed health decisions. Dr. Suwannarat, thank you so much for being here.

Pim Suwannarat, MD: Happy to be here. My pleasure, Dr. Williams. I'm really looking forward to our discussion today.

Host: Yes, agreed. I have so many patients that come in asking about genetic testing and when it's right for them. So, we always like to start with the basics. What role does a person's gene play in cancer risk?

Pim Suwannarat, MD: I like to say all cancer is actually due to changes in our genes, but it isn't always due to inherited changes or inherited what we used to call mutations, right? And those inherited genetic mutations or variants account for maybe around 10% of cancer occurrences. The rest of the time, cancer happens due to those multifactorial causes that we hear about, things like diet and exercise and environment, exposures, that combination altogether.

There might be some minor family traits, but not those clear-cut genetic risk factors that we know about. You might have heard about like the BRCA1 and 2 genes, and maybe patients even ask about that. Within that group, probably about 10% of cancer. And we used to think it was lower. But now, because genetic testing is so advanced and we know so much more, that keeps on creeping up

Host: Yeah. And I know my patients are so glad about how much research is being done. BRCA1 and 2 come up a lot in conversation. So when should genetic counseling or genetic testing be considered for cancer risk?

Pim Suwannarat, MD: So, certainly if you have had cancer yourself, you might want to look into whether genetic testing is appropriate for you or not. Your oncologist or surgeon is a good place to start. Even your primary care doctor can be a really good resource. If you haven't had cancer yourself, and you're just worried about your family history, there are certain things that as geneticists and genetic counselors, we would look at that might be a little bit concerning and suggest that you should look into things in more detail.

Host: Yes. Thanks for the primary care plug because I feel like, for me, being a primary care doctor, that's where a lot of these discussions start is with a routine physical or a health assessment where we're going through the family history. And so, I always like to say, when you're preparing for an appointment with your physician, make sure you write down notes and questions that you may have for your upcoming appointment. How do you suggest a person prepare for an appointment or a meeting with a genetic counselor?

Pim Suwannarat, MD: Right. So of course, again, family history, but getting the specific details is really important. If there are people in your family that have had cancer, we want to know what type of cancer—very specifically, which organ. Cervical cancer is different from uterine or womb cancer, is different from ovarian cancer. And they're all female-type cancers, right? But they're all very distinct, and they have very different hereditary and environmental causes. So, knowing your family history, the specific type of cancer, the age that that person was diagnosed with cancer. And how you're related to them. Is it your mother? Is your mother's brother or sister? Is it your grandparents on your mother's side? On your father's side?

And I think one really important thing, sometimes people miss, I would say less now than maybe 10, 20 years ago, is that your father's family history of cancer and the history on his side of the family is just as important as the maternal side. We're so used to thinking breast cancer in females, but those genes that are associated with cancer risk, including the BRCA1 and 2 genes can be inherited either from your father or your mother.

Host: Okay. So, you've prepared for your meeting with the genetic counselor. Thanks for walking us through that. How is genetics testing done and what genes are commonly tested?

Pim Suwannarat, MD: Yeah. So, we can do genetic testing from either blood, saliva, or cheek swab sample, which means you have the option of coming into a Kaiser lab or doing the testing at home with a kit that we mail out to you. And the testing that we're doing usually includes a core panel of genes. For example, those BRCA genes, genes associated with colon cancer, and a couple of other cancers, the panel that we most commonly use has around 40 genes on it. So, it's a pretty big panel.

Host: I always tell my patients, just do the best you can collecting as much data as possible, right? Because sometimes we don't know all the details, but as much information that you collect for your appointment is important and helpful.

Pim Suwannarat, MD: Absolutely. We don't need to know like the pathology, but at least the organ. And even when you're thinking about age, you know, it's hard to know our family members age at diagnosis, but I like to use age 50 as kind of a cutoff. If a cancer happens before age 50 that feels like it's at a young age. And in people that are over 50, as far as cancer occurrence goes, that is less likely to be associated with an inherited genetic cause. I don't like to say 50 and over is older. I don't think that's the case at all. But when we're thinking about cancer occurrence, that 50 is a nice number to have in mind.

Host: Got it. Okay. So, we've met with the genetic counselor. You've gotten your test results back. Can you talk a little bit about what it means to have positive, negative, or even unclear results?

Pim Suwannarat, MD: Right, right. So, genetic testing is complicated. And there are different types of results. I think it's important to start with all of us have two copies, for the most part, for all of these genes, right? So, I have two copies of the BRCA2 gene. I have two copies of the BRCA1 gene, but the differentiating factor, or the importance is whether there is a change, what we used to call a mutation. And nowadays, we call it pathogenic variant in the gene. And I like to compare pathogenic variants and changes in our genes to, like, spelling errors. So when we're doing genetic testing, what the lab is doing, it's looking at the spelling of the genetic code for any changes, any variations. And then, they're determining whether that variation is actually problematic or not, right?

And my favorite example is, you know, if you are spelling the word grey, G-R-E-Y, you can also spell it G-R-A-Y. So, there's a variation, an E and an A, but the meaning is the same. So, the lab doesn't even report that kind of variation. Now, if we spelled the word G-R-E-Y, and then for some reason, the spelling was changed to G-R-E-G, Greg—Greg and grey, that's really going to cause a problem. So, that's a pathogenic variant, right?

And then, you have genetic changes, and I'm going to change my word now. So, the word color. You can spell it C-O-L-O-R, and you might know that in the UK system, that could also be spelled C-O-L-O-U-R. So now, we have a problem, right? The word, it's both read color, the meaning is the same, but we don't know if that extra U is going to cause any issues or not. It might not at all. And that's what we call a variant of uncertain significance.

So when we're doing that genetic testing, looking at those copies of genes that all of us have, it's basically a spell check. If there is a change in the spelling that is known to be significant, that's a pathogenic variant, what we used to call a mutation. If there are just normal types of variation that are known to be seen in the human population, those aren't even reported out. That's what we call a negative or normal genetic testing result. And then, there are those variants of uncertain significance.

Host: I love these analogies. This is very patient-centered and I really think it helps explain this complicated theme, but very basic terms to help us understand what's going on in our bodies. Okay. So, we've gotten the results. What do patients do once they've gotten a positive result that says, "Okay, you are at risk of this cancer X or Y"?

Pim Suwannarat, MD: So, I think that's a great point, is that it's the positive results that are really significant and can impact your healthcare and screening. So many questions that just pop up in your brain, right? But the variants of uncertain significance, we treat them similar to negative or normal results.

So before I get to the positive results, I would mention that even when you have a negative or normal genetic testing result or a variant of uncertain significance, if there is a strong family history of cancer in your family, you still should go over that information with your primary care physician, because there are screening options that are modified based on your family history alone without even looking at the genetic testing results. And I think that's really important. We get so focused on genetic testing. It's so cool. It gives you so much information. But ultimately, going back to that family history is really important.

Host: So important. And I know specifically for breast cancer and colon cancer, you know, most of the time we don't need genetic testing. It's really just based on your family history when we need to change our screening for you.

Pim Suwannarat, MD: Absolutely, absolutely. If you have a family history of colon cancer, it doesn't really matter. If there's a positive genetic test result, you're going to need a colonoscopy, The genetic testing result, if it's positive, it might change the frequency a little bit, but you're still going to get a colonoscopy.

I think the one example of the breast cancer that's really important is. You know, the genetic counselors can run risk calculation models, and those models don't look at genetic testing results. They pretty much look at your own history, things like when you started your menstrual periods, how many children you had, if you've ever been on any hormone therapy. Those models, combine that with your family history mostly of breast and ovarian cancer. And that calculates your risk for breast cancer to develop over the lifetime.

If your genetic testing is normal, or maybe you don't want genetic testing. But your calculated risk is over 20%, then you could think about adding a breast MRI into your mammogram screening.

Host: I think that's the beauty of our integrated care model, is that when our patients and members come in for their routine health assessments or physical, when we're going over that family history and, you say, "I have this relative that had breast cancer," okay, well, we need to schedule a phone appointment with our genetics team so that you are going through that risk calculation with them to determine if we need to do the breast MRI imaging in addition to the mammograms.

Pim Suwannarat, MD: Absolutely. Absolutely. And I will say it's not uncommon that based on family history, people don't meet our current criteria for authorization for genetic testing. But they still might have that high-risk of cancer. So, there really are those two aspects when we're thinking about our risk for cancer overall.

Host: So once we get the genetic testing result, how can genetic testing help them take action on their health?

Pim Suwannarat, MD: Yeah. So based on the result, if there's a positive result, that already provides information right there on which types of cancer you might be at risk for. And it's important to know that it's a risk for cancer, not a definite diagnosis of cancer. And then, based on those specific cancer risks, we can come up with a screening plan to reduce your risk of cancer.

Host: Great. And about how long does it take you guys to get the results and respond to patients once we get the results in?

Pim Suwannarat, MD: So after you've had your blood drawn or sent your cheek swab kit back in, the results are usually back in the system within one to two weeks. Once the results hit our system, we try to get back to you within one or two business days and make sure that we're closing a loop with you.

Host: All right. Well, thank you so much for this information. We learned a lot about when genetic testing is beneficial and when we can learn from it. Here are the top takeaways. One, most cancers are not inherited, but genetic testing can help identify people with a higher hereditary cancer risk. Two, a strong family history of cancer, rare cancers, or early cancer diagnoses may be reasons to consider genetic counseling. Three, genetic testing is usually simple using blood, saliva or cheek swab samples. And results can guide next steps. Four, a positive genetic result does not guarantee a future cancer diagnosis. But it can help people take preventative action through earlier screenings and healthier choices. And five, sharing genetic test results with family members can help them better understand and manage their own cancer risk.

For more information from our experts, visit kp.org/doctor and listen to more episodes of Healthier You wherever you get your podcast. If you enjoyed this episode, be sure to share it with others and subscribe. Have questions or health topics that you would like to discuss? Let us know in the comments. From all of us at Kaiser Permanente, be well.