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In this podcast, Cancer.Net Specialty Editor Dr. Petros Grivas talks to Dr. Marianne Dubard-Gault about what people with bladder cancer should know about genetics and genetic testing, including what information genetic testing can provide, how it can inform bladder cancer treatment, and what to expect when meeting with a genetic counselor.

Dr. Grivas is a medical oncologist at Seattle Cancer Care Alliance, clinical director of the Genitourinary Cancers Program, and professor at the University of Washington School of Medicine. He is also an associate member of the Clinical Research Division at Fred Hutchinson Cancer Research Center. Dr. Dubard-Gault is the medical director of the Cancer Genetics Program at Fred Hutchinson Cancer Research Center and an assistant professor at the University of Washington School of Medicine.

View disclosures for Dr. Grivas and Dr. Dubard-Gault at Cancer.Net.

Dr. Grivas: Hello, I'm Dr. Petros Grivas. I'm a medical oncologist and serving as the clinical director of the Genitourinary Cancers Program and professor at the University of Washington Fred Hutchinson Cancer Center. I'm very excited and thrilled today to discuss with one of the amazing leaders in the field of cancer genetics, Dr. Marianne Dubard-Gault, who is my colleague here at UW Fred Hutchinson and has been such a wonderful human being and advocate for her patients and also really a key opinion leader in the field of genetics and the implementation in patient care. Dr. Dubard-Gault, welcome, and I will let you introduce yourself.

Dr. Dubard-Gault: Thank you very much, Dr. Grivas, and it's a pleasure to be here. So thank you for the invitation. I am Dr. Marianne Dubard-Gault. I am a trained oncology doctor and a trained genetics doctor, and my focus now, as Dr. Grivas mentioned, is in the cancer genetics world where I help people either get genetic testing in the first place and/or their family members have interventions for their screening and early detection. I'm also an assistant professor at Fred Hutchinson Cancer Center in Seattle, Washington, and then at the University of Washington on the other side. And I lead the Cancer Genetic Survey Center at Fred Hutchinson Cancer Center. And I have no disclosures.

Dr. Grivas: Thank you so much, Marianne, and again, thank you for helping our patients. And I'm really, really excited today because it's a very important topic, not frequently discussed. And I really, really wanted to make this happen, and thanks to Cancer.Net for helping us getting the word out there. I have no relevant disclosures in this topic. My disclosures are listed on the ASCO website. And Marianne, I will start us off by asking you, just for the audience to set the stage, can you define what we call “genetics”? What exactly are we referring to?

Dr. Dubard-Gault: Yes, that's actually very important. That's probably the first thing that happens in the clinic when we talk to patients is, what is genetics anyway, right? So genetics is the study of the DNA or the genetic makeup that we all have. And that makes a person who they are, right? So looking into the genetic makeup to make sense of it and inform treatment or other interventions.

Dr. Grivas: Thank you much, Marianne. And I think it's so important again for our patients to understand the definitions here. So let me ask you, can you define the difference between a genetic mutation versus genetic alteration? How would you explain that to a patient?

Dr. Dubard-Gault: I think about them in a similar way. So, to me, a genetic mutation or alteration is a spot in your DNA. So there's a long stretch of letters, and there's a spot in there that either was copied or wasn't copied properly over. And so that leads to a command that kind of not being executed properly. And so an example of that would be if I gave you the 2 words “red” and “bed,” those 2 words would mean totally different things in your mind. And so if you were supposed to hear “red” and you heard “bed,” then downstream will be a different outcome.

Dr. Grivas: Thank you so much, Marianne. And this is very important because for the audience as you pointed out nicely, the genetic code, the DNA translates a message, alright, that becomes a protein and eventually a function of the cell. So if that code, if that message is misspelled, it can lead to different altered and changed-up protein for the cell. That has implications and can potentially predispose someone to cancer. So if we can also help the audience understanding the differences between what we call “somatic genetic mutations” and “germline mutations.”

Dr. Dubard-Gault: Absolutely. And this is also something that comes up every time because they're part of the same groups of things overall, right? So somatic means tissue or tumor. And germline, or hereditary, sometimes you'll hear that word interchangeably means inherited or hereditary or part of the genetic makeup or the code that you were born with. So different parts of our body have different genetic mutations. And that is why even with 2 identical twins, they won't have the same moles on their skin, or they won't have the same medical conditions, even if they have exactly the same genetic code. And it's exactly the same for a person who has a tumor, right? The DNA or the genetic makeup they were born with will stay exactly the same as they grow older, but the genetic makeup their tumor has as the tumor grows can change and make more or have more mutations. So testing different parts of the body will help tease out which ones of the mutations are located where? Is it in a tumor only? Is it in the genetic makeup you were born with or is it part of that transition between the 2?

Dr. Grivas: Thank you, Marianne. I think this is great when we explain to the patients what exactly mutations, alterations, means, and the difference between a somatic tumor testing, as you said, mostly to help define treatment options. And what you very nicely discussed are germline testing, looking at hereditary predisposition to cancer that can impact the patient and also family members and the broader family. And one kind of take-home message may be for our audiences, when someone is about to see an oncologist or their provider, is greatly helpful if they can do quote-unquote "their homework" and try to understand and delineate and capture as much as possible regarding the family history. And sometimes it's hard, especially when you go to distant relatives, cousins, nephew, nieces, it's more difficult, but it can help a lot and inform that discussion and whether a referral to a genetic counselor or geneticist is relevant. So that's what we try to do with nurse navigation these days to help inform people with cancer before their appointment how they can maximize to capture that information, it can be helpful to them and for the provider. And the next question, Marianne, is how common are these genetic germline mutations in people with bladder cancer?

Dr. Dubard-Gault: I think the answer is still out there. We don't have the complete answer today. We don't know all the genes that are implicated in bladder cancer today. So given that, we probably don't have the full or complete answer as to how many people with bladder cancer would have it. But kind of to get close to the answer, as close as we can possibly be today, I think it depends on the group of patients with bladder cancer that you test, but I would probably give a 1 in 10 people with bladder cancer would have an inherited genetic mutation.

Dr. Grivas: And that's very helpful Marianne. And of course, varies, of course, across the different scenarios and the family history as you mentioned, the age of cancer diagnosis. And sometimes it's interesting in patients with urothelial carcinoma, cancer in the upper urinary t