Julie Ann Sosa, MD, MA, FACS, Professor of Surgery and Medicine, Chief of Endocrine Surgery, Head of the Endocrine Neoplasia Diseases Group, Co-Leader of the Solid Tumor Therapeutics Program at the Duke Cancer Institute, Director of the Surgical Center for Outcomes Research in the Department of Surgery, talks about the possible connection between thyroid cancer and flame retardants.
Interview conducted by Ivanhoe Broadcast News in October 2017.
Let’s start with thyroid cancer itself, is it very common, is this something that you’re finding a lot of people are dealing with in this country?
Dr. Sosa: Yes. There’s a virtual epidemic of thyroid cancer that is being seen in the United States, and many would argue it’s a pandemic because similar trends are being seen around the world, in almost every developed and developing country. In the United States over the last thirty years, the incidence of thyroid cancer has more than tripled, and if anything, perhaps it is accelerating. Right now, in 2017, thyroid cancer is the fifth most common cancer among American women. It is anticipated that by 2019, it will overtake both colorectal cancer and uterine cancer to become number three in women. And already it is the most common cancer in women under the age of thirty five. It’s primarily a disease of women; about three quarters of all patients with thyroid cancer are women. The engine for the increase in incidence is one specific histologic type – papillary thyroid cancer. Papillary thyroid cancer now represents nearly ninety percent of all new cases of thyroid cancer. In summary, the epidemiology of thyroid cancer is rapidly changing, and it is a public health issue. I think the challenge for those of us who are scientists in the area is to understand the genesis of the observed changes, because I would argue the best form of treatment would probably be prevention. Many have argued that the observations about increasing incidence are artefactual and really just the result of over-diagnosis or surveillance bias; that is, we are performing more and more CT scans, ultrasounds, PET scans, and MRI’s; we have a low threshold for imaging our patients, and as a result of doing so many radiology studies, we incidentally identify thyroid nodules that ultimately prove to be small, clinically insignificant thyroid cancers. This was the prevailing belief until earlier this year, when a group of investigators at Duke University and the National Cancer Institute published an important study in JAMA. Together with Dr. Cari Kitahara, who was the senior author of this study, we demonstrated that the incidence of thyroid cancer in the United States is indeed increasing, and it is not just small cancers that are becoming more common. Cancers of all stages and sizes are being diagnosed, including the largest cancers and those that are most advanced in terms of locally advanced and metastatic disease. What was particularly surprising in our study is that we also observed that the incidence-based mortality rate of thyroid cancer is increasing significantly, suggesting that this is real, and more people are dying of the disease. In fact, thyroid cancer is one of just a few cancers where we are losing ground in the United States; I believe it is number two behind only liver cancer in terms of this increase in mortality. Based on these collective data, we decided to focus our energies on trying to explore other potential causes or explanations.
This set off some alarms basically?
Dr. Sosa: Many patients with thyroid cancer have heard the phrase, “Thyroid cancer is the good cancer.” For those of us who study thyroid cancer and certainly for patients who have thyroid cancer, this is an oxymoron, since there is no such thing as a good cancer. I think people who say this are not malicious; what they mean to say is that most people don’t succumb to the diagnosis, which is true, but instead they live with their disease. Since the disease usually does not kill patients, patients must live with this diagnosis for decades, and over that period of time, they are assessed the costs of surveillance, remedial surgery or medical treatment with radioactive iodine. As a result, thyroid cancer is one of the cancers most closely tied to bankruptcy of patients and their families. The effects of the disease are profound; while they rarely include mortality, costs can be formidable over the course of a patient’s lifetime.
When you mention causes, this is what started your research or some of the research here at Duke, so what were you and your team looking at as far as possible causes and describe what that is.
Dr. Sosa: There are a few causes of thyroid cancer that have been well studied and proven to be associated with thyroid cancer. Those include things like radiation to your face, neck or chest, particularly when people are exposed in childhood and adolescents. A family history of some thyroid cancers is definitely a risk factor for the disease. Having thyroid nodules or a history of thyroid dysfunction are also factors known to be associated with the disease. But many of us believe there are other factors that have almost certainly gone unrecognized, or at least less well understood. One example would be obesity; there is now very good population level data which suggest that obesity is associated with a number of different cancer diagnoses, including thyroid cancer. Indeed, this is an active area of investigation at Duke. But the one consideration that really fascinated us was potential exposures in the environment, which we like to call the exposome. The exposome is the world you travel in and inhabit; whether it’s your home, your workplace, or the vehicles in which you travel from one place to another, like your car, a bus, a train, or a plane. I was having a conversation with some of my colleagues in endocrinology and at the Nicholas School of the Environment. The faculty there are called environmental scientists. We made a random – but I think critically important – observation that the chemical structure of several flame retardants that can be found in the home bare a remarkable resemblance to thyroid hormone. The molecules look very much alike, with just a few small differences. So we asked ourselves the question: Could there be mimicry going on? That is, is it possible that these chemicals, flame retardants, that are in your home acting like thyroid hormone, mimicking it, and in so doing, could they potentially be altering the way the thyroid gland works or functions? If we know thyroid dysfunction is associated with thyroid cancer, is it possible that they are influencing the risk for the development of thyroid cancer. So it started with sort of serendipity in our meeting, and then the observation made about a chemical structure, and that was the start of the study.
So you’re saying the thought process is that these might be working as an endocrine disruptor?
Dr. Sosa: Correct.
People don’t realize that these flame retardant chemicals are in everyday things in our home, what types of items are we talking about?
Dr. Sosa: Yes, the other interesting observation you can make is over the last several decades while the incidence of thyroid cancer has been increasing, the use of flame retardants has overall increased as well, and for good reasons. They importantly help to reduce the risk of fire, and that’s really important for safety in the home or the workplace. So the question is, is an increasing use of one flame retardant potentially associated with this observation of an increase in incidence of cancer. These chemicals, the flame retardants, are located in many different things in the home, ranging from upholstery (like in your sofa, drapes, and curtains) to the insulation in the walls of your home, and in plastics. And they’re also located in electronics; for instance, everything that is black (this is a little overly simplistic, but anything black in an electronic device, so, say, a flat screen television) often contains flame retardants. Different flame retardants are in different items in the home, and different mixtures of flame retardants are located in these different items in your home.
How would that be transmitted, are we breathing it in or what’s going on there?
Dr. Sosa: So yes, it’s very interesting. They leach out of these structures over time, and some of these flame retardants have been shown to have harmful effects on the body. One that we studied is called BDE209, or decaBDE; it was phased out in 2013. But you still see it present in people’s homes, and when we conducted the study looking at a potential association between flame retardants and thyroid cancer ,the way we measured these exposures was through something I never thought I would do because I hate doing it, but it was by vacuuming people’s homes. This is something that our environmental scientists apparently do a lot, and they have a very special vacuum. And what they did was go into people’s homes with their permission and with institutional review board approval, and they literally cleaned their house for them with the vacuum. And when you take the dust from the home and you study it with very special tests, you can dissect out levels of individual flame retardants, and you can also look at mixtures of these flame retardants. So that was the way that we measured cumulative exposure.
So really possibly in our house dust which we all seem to have, that really could be the culprit?
Dr. Sosa: Yes, so that’s one way that we can measure it and that it can accumulate. And then what could happen of course is that when you touch things in your home, it can get on your hands, and from your hands, you touch food and other things that ultimately you ingest; that is probably the most common route. Some people have postulated that maybe if you wash your hands all the time you can try to block this route, but that’s been poorly measured and poorly studied.
So really is there a way to protect yourself from these chemicals?
Dr. Sosa: I don’t think so, because first of all, many of these chemicals have very positive influences in our lives. The question is, are there some under-studied harmful effects, particularly in the arena of cancer. I would say that we should not become alarmists and suggest risks outweigh benefits; rather, I think the challenge as a scientist is to try to understand what the potential association might be between the flame retardants and (potentially) thyroid cancer. Second, what is the mechanism by which this association might be happening, Because that is what would inform the answer to your question about what to do about it.
You’re saying we also have to look at the patient as well?
Dr. Sosa: Absolutely. That’s what we did as a first step. Many might say ‘wow,’ you sort of took an opposite approach to what most people do. Many people start with a question, and they start in the laboratory by studying animal models, whether that’s in a mouse or a rat or a primate or a dog. We started with a problem; meaning an actual problem which is the epidemic of thyroid cancer; therefore, we decided to start with humans, and what we did was a case-control study. Simply put, we took a hundred and forty subjects: seventy were patients with papillary thyroid cancer that had been newly diagnosed at Duke, and we matched them to seventy healthy patients who had no evidence of either thyroid disease or thyroid cancer. We matched them to make sure that in all ways that we could measure they appeared to be similar, in terms of age, gender, and socioeconomic status. We also strove to assure they were similar in terms of their body mass index or weight, because one thing we know is that fat or adipose tissue can influence the accumulation of these flame retardants in the body. So we matched these two groups of seventy patients for a total of a hundred and forty patients. They were comparable in all measurable ways. This is a small study; it is not a large study, and it’s a first study. And then we measured levels of different chemicals in flame retardants, as well as thyroid hormone levels from blood that we collected from the patients, from urine that we collected from the patients and the controls, and most important, the dust that we vacuumed from their homes. What we discovered is that for three of the flame retardants, the levels were significantly higher in the homes of patients with papillary thyroid cancer compared to the controls. We also discovered – which is very interesting and which we’re not yet sure what it means – is that is appears that the severity or the aggressiveness of the thyroid cancer was also associated with the flame retardant exposure, and the presence or absence of a mutation called the BRAF V600E mutation was differentially expressed in thyroid cancer tumors based on exposure to some of these flame retardants. And what we know about this specific mutation is that it is present in about half of all new cases of papillary cancer, and it’s a marker for aggressiveness of the cancer, so it’s a very interesting and complicated clinical picture that really needs to be further studied.
The patient that we spoke with; tell us about the bracelet he wore for a week and what you were looking for with that?
Dr. Sosa: Based on the initial results from our first study, which has been published and which has gotten a lot of media attention, we are now doing a follow-up study as a next step. One question for the follow-up study is can we replicate the results of the first study in a larger group of patients? More important, or at least as important, is were we overly restrictive in just looking at flame retardant levels in people’s homes? What we know is that many Americans spend most of their time at home, but many Americans spend a lot of their time outside their home. There are some of us, like me, for example, who spend probably most of my day at work. Many of us travel from work to home and back, we travel for fun and vacation, and we travel to see family. And in all of these places, in our work place, in our cars, in our buses, in our trains, in our planes as well as in our homes, we are being exposed to a number of different chemicals and flame retardants. So the question is, is the cumulative exposure to flame retardants different than that in the home and its potential association with thyroid cancer there. How do we measure dust or exposure in all these places? We can’t really take vacuums onto city buses or vacuums into Duke University. And so the creative solution to this problem was from Dr. Heather Stapleton, who is an Associate Professor and an environmental scientist here at Duke at the Nicholas School. Her group developed wrist bands that are very cool; a lot of people wear them for other purposes, to support breast cancer and thyroid cancer and pancreatic cancer. But we’ve asked our patients to wear them because they go with the patient everywhere and they measure flame retardant exposures. There’s really no risk to patient, and they wear them for seven days; they don’t take them off, they wear them in bed, they wear them in the shower, they wear them at work, they wear them at home, and everywhere they go. Then they mail them back to us, and we use the wrist bands to measure the total exposure to flame retardants over a week for each patient. And it’s really cool, Dr. Stapleton’s group had to develop these wrist bands. One of the really creative, innovative ways she did it was first by studying collars on pets. I have a rescue dog named Mary Pink, and Mary Pink wore her special collar made like the wrist bands, which trialed the technology that is now being used in the human bands. The reason why we used pets is that we know pets can be a really good model for environmental exposures in the home because they tend to spend most of their days and nights in the home. Because they groom and lick, they potentially ingest a lot of these flame retardants and absorb them, so pets served as a model in a number of different ways for the study we’re now doing in humans.
So that is where you all are with the study itself and now you will wait for results from the bracelet analyzing that?
Dr. Sosa: Exactly. Right now, we’re busy recruiting patients at Duke in the Cancer Institute and affiliated clinics. We’re recruiting both patients with papillary thyroid cancer as well as healthy controls. We’re also looking to validate our findings in a separate cohort of patients at a population level outside of the Durham area. And finally, we’re now starting to get ready to move into the basic science laboratory to try to study in a mouse model the mechanism by which flame retardant exposures may be increasing the likelihood that you develop thyroid cancer.
And that could possibly unlock some more answers and possible treatments?
Dr. Sosa: Possible treatment or if we can find factors, exposures in the exposome, that could be modified or even eliminated, then there’s even a potential opportunity way down the road to prevent some forms of thyroid cancer.
Is there a specific website if patients were interested or wanted to learn more about this?
Dr. Sosa: What I would say is patients or people interested in the topic who would like to volunteer as a control or as a patient could contact me at Julie.Sosa@Duke.edu, or Dr. Heather Stapleton, who is my co-principle investigator, at Heather.Stapleton@Duke.edu.
So this is a fascinating study.
Dr. Sosa: I think many of us think about science in very traditional ways. We think about laboratories with test tubes and beakers and mice. Other people think of science as clinical research, where there are patients and drugs being administered. I think a lot of the innovation and discovery will be like this kind of study, where we’re going out into the exposome, into the habitat where we actually live and work, to understand the world we live in and the way it influences us as potential patients. We have to broaden our horizon as to what defines science.
You believe this could be a trend for the way science will be looked at you’re saying instead of being isolated in a lab somewhere?
Dr. Sosa: I hope so. Science can’t be remote; it has to be really, truly bench to bedside. I don’t know about the vacuuming part, though! It’s very interesting, we also asked patients a lot on a questionnaire about what they do, where they spend their time, how much time they spend on a computer, watching television, and sitting on their sofa. We got a lot of information about lifestyle and how people modify exposures. And when they vacuumed the home, they really focused their energy in the part of the home where people lived. Like in my home, we all collect in the kitchen; that’s just what we do. We like to cook, we like to eat, our friends like to cook and eat. But for other people, they like to spend time in their living room watching television or playing computer games. And so we collected this kind of detailed information in a personalized way to inform the science that we conducted. And I think that’s the creativity of what discovery is, right? Science can be super cool.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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Julie Ann Sosa, MD, MA, FACS
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