Name:
A 39-Year-Old Healthy Male
Description:
A 39-Year-Old Healthy Male
Thumbnail URL:
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Duration:
T00H08M34S
Embed URL:
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Content URL:
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Upload Date:
2022-02-28T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[upbeat intro music]
DR. HANDY: Hi, welcome to Harrison's Podclass where we discuss important concepts in internal medicine. I'm Cathy Handy.
DR. WIENER: And I'm Charlie Wiener and we're coming to you from the Johns Hopkins School of Medicine.
DR. HANDY: Welcome back to Harrison's Podclass. We are excited to be back for season number 2.
DR. WIENER: We have lots of exciting new questions and some new topics. And we're going to start with a new topic for this season.
DR. HANDY: All right, this is Episode 49: A 39-Year-Old Healthy Male.
DR. WIENER: A 39-year-old man comes to your primary care clinic for his annual routine physical. He reports no new symptoms or problems from the year prior. He takes no medication, but has taken your advice and started wearing a step monitor. His physical examination is normal and his BMI is 20. He recently saw a TV commercial and asked for genetic testing to determine his risk of cancer.
DR. HANDY: I've seen lots of those commercials too. So I do know what he's talking about. Direct to consumer advertising of genetic testing products seems to be quite prevalent now. And the commercially available products only have a very limited number of cancer-related genes and really should not be used for medical decision-making. And they're not supposed to be used for that. He is being a good patient though and asking his doctor about it and not just using the test on his own.
DR. HANDY: Does he have any history of cancer though? Or something that would prompt you to consider referring him to a genetic counselor?
DR. WIENER: So he has no personal history of cancer. His paternal grandfather, a heavy smoker and a coal miner died at the age of 74 of lung cancer. That's his only risk of cancer in the family. His parents and his two siblings are alive and well and he has no other family history that's relevant to cancer or other acquired genetic diseases.
DR. HANDY: So he's never had cancer. And it does not sound like he's at risk of an inherited cancer. The cancer that you mentioned in his paternal grandfather, who you mentioned was a heavy smoker and a coal miner and had lung cancer. That to me, sounds like a clear environmental exposure that likely contributed to the risk of his cancer.
DR. WIENER: Okay, so the question's asking, and my question for you is, what do you tell him regarding genetic testing for his cancer risk? And here are the options
A: yes, you should have it given your family history genetic testing would be recommended;
B: yes, given your age, genetic testing would be recommended;
C: no, because you are not old enough for genetic testing;
D: no, because you do not have risk for a familial cancer syndrome;
E: no, because our office has not started cancer screenings yet.
DR. HANDY: So let's talk about who we generally want to consider for genetic testing. And then we can go into whether or not he fits into that population.
DR. WIENER: All right.
DR. HANDY: First, I think of patients who have certain cancers themselves at early ages of onset. So for example, if he presented with prostate cancer in his 30s or 40s, that would be very atypical and in that setting we would want to refer him for genetic counseling because we would not expect a 30 or 40-year-old to develop prostate cancer. The second group I would consider is a patient from a family with a known cancer syndrome.
DR. WIENER: What do you mean by that?
DR. HANDY: In inherited forms of cancer or what we consider cancer predisposition syndromes, one ileal of a particular tumor suppressor gene is inherited in mutant form. Individuals with the inherited form have a headstart, so to speak, on the development of cancer. Meaning that they already have one ileal mutated from conception and only need one additional mutation to initiate the process. For example, if this patient's grandfather had colon cancer and you learn he was diagnosed with a germline mutation in the APC gene, that's the gene that causes familial adenomatous polyposis.
DR. HANDY: If that was discovered in a relative, you would want to test for that in the patient because that's one of the cancer predisposition syndromes and familial or inherited forms of cancer. Lastly, if there was a family history of multiple cancers, I would consider genetic testing. So for example, if his sister had breast cancer, if his mom had ovarian cancer, if his maternal grandfather had prostate cancer, those could all be related by a common genetic alteration so you might consider genetic testing in that case.
DR. HANDY: Although I would add you would want one of the affected family members, so one of the family members who had cancer, to be tested first.
DR. WIENER: Okay, but recent technological developments have made it feasible to obtain high quality sequencing of all the protein coding DNA sequences and even the entire genome in any given individual. And it's not that expensive anymore. So genetic testing has gotten a lot easier to do and a lot cheaper because the cost of sequencing has gone down. Why not just do it in everyone?
DR. HANDY: The redundant nature of modern DNA sequencing provides an extremely high level of sensitivity, such that mutations and polymorphisms will inevitably be identified. In patients lacking a clear family history the significance of these DNA sequence findings is not always apparent. So even mutations in tumor suppressor genes are difficult to interpret unless there's an obvious functional implication.
DR. HANDY: For example, the truncation of the open reading frame or that particular mutation has previously been associated with cancer. Such germline mutations are very rare in the general population. What's much more common are variants of unknown significance or VUSs. Now, when VUSs are found during genetic testing, it can't be used to evaluate the relative risk of cancer but nonetheless can cause anxiety because they represent a deviation from the reference ileal that's established as what we consider right now normal.
DR. HANDY: And because of the low yields of informative mutations that modify cancer risk and the frequent identification of VUSs, it's generally not appropriate to use DNA sequencing to assess cancer risk in individuals unless the family history or the personal history is suggestive of a germline mutation.
DR. WIENER: Seems likely that with further research we're going to clarify a lot of these VUSs and more information. So this is a field that we probably have to stay pretty close to, right?
DR. HANDY: Yeah, absolutely. And the answer to this question and what we are doing might totally be different in five years from now.
DR. WIENER: So given the current state of understanding, what do you do if a test is positive?
DR. HANDY: The other thing to point out is the impacts of a positive test when appropriately done. So a positive test may lead to alteration of clinical management. Such as either increased frequency of cancer screening and when feasible and appropriate, prophylactic surgery. There are also substantial potential negative consequences of even a true positive test including psychological distress, causing anxiety and depression and discrimination.
DR. HANDY: Although the Genetic Information Nondiscrimination Act does make it illegal for predictive genetic information to be used to discriminate in health insurance or employment. We know that in some screening procedures, like CTs for lung cancer, there's a substantial burden of false positive results. In general, we have to be careful about recommending screening tests, particularly in low risk individuals.
DR. HANDY: And with the growing number of genetic tests screening should not be conducted without counseling before and after disclosure of the test results.
DR. WIENER: Okay, so you've made the case that genetic testing should not be done in this patient. Why are the other answers not correct?
DR. HANDY: Age alone doesn't really impact whether or not you should undergo genetic testing for cancer risk and your cancer screening habits also wouldn't affect genetic testing. The reverse is true where your genetic test results might impact your cancer screening habits though.
DR. WIENER: Okay, what about that stool test that's been all over the television?
DR. HANDY: So that test does test for some common somatic mutation. So those are acquired mutations generally in colon cancer. And it also tests for occult hemoglobin. So it's not a genetic test in the way that we've been talking about it, where it looks for germline mutations. Again, it would not be appropriate for this young man who doesn't have an increased risk of colon cancer.
DR. WIENER: So the teaching point is that patients who are from a family with a known cancer syndrome, from a family with a history of cancer or have an early onset of cancer may be candidates for genetic screening. However, patients should not undergo these genetic screening tests without qualified genetic counseling as part of the care delivery model.
DR. HANDY: And you can read more about this in the Harrison's chapter on cancer genetics. [outro music] [Mr. Shanahan] This is James Shanahan, publisher at McGraw Hill. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. go to accessmedicine.com to learn more.