Why are colorectal cancer rates rising among younger adults? Could chronic inflammation, modern lifestyle, diet, environmental exposures, and emerging contaminants such as micro- and nanoplastics be contributing factors? What does current science actually know—and what remains uncertain?

In this episode of the ALLATRA Global Research Center Podcast, Dr. Karolína Hronová, Clinical Pharmacologist, Environmental Health Researcher at the ALLATRA Global Research Center and Dr. Jeffrey Long, Radiation Oncologist and Expert in Human Health Impacts of Environmental Factors have a conversation with Dr. Lorne J. Hofseth, Professor and Associate Dean for Research at the University of South Carolina College of Pharmacy and Director of the Center for Colon Cancer Research, who shares insights from decades of research on chronic inflammation, colorectal cancer, environmental risk factors, and cancer prevention. His research focuses on understanding how chronic inflammation, diet, the gut microbiome, DNA damage, and environmental exposures interact to influence cancer development and human health. 

The conversation explores the global rise of early-onset colorectal cancer, the biological mechanisms linking chronic inflammation to cancer development, and the growing scientific interest in the role of the exposome, the cumulative environmental and lifestyle factors that influence human health throughout life. Dr. Hofseth also discusses the current evidence on micro- and nanoplastics, emphasizing what research has demonstrated so far, where important uncertainties remain, and which questions future studies must answer.

In this episode:

• Why is early-onset colorectal cancer increasing worldwide

• Chronic inflammation as a driver of cancer development

• Environmental exposures and the concept of the exposome

• Diet, obesity, and the gut microbiome in colorectal cancer risk

• What do current studies say about the potential impact of microplastics and nanoplastics on the development of cancer

• What scientists still do not know about environmental risk factors

• Cancer prevention and the future of environmental health research

Learn more about Dr. Lorne J. Hofseth:

https://sc.edu/study/colleges_schools/pharmacy/faculty-staff/hofseth_lorne.php

Report of the ALLATRA Global Research Center “Nanoplastics. A Systematic Risk Analysis for Human Health, Ecosystems, and the Environment”

https://allatra.org/global-research-center/publications/agrc.report.mnp.2026.04001

The podcast is hosted on the ALLATRA Global Research Center platform.

This material is provided for informational and discussion purposes only. The statements, assessments, interpretations, conclusions, and hypotheses expressed represent the personal views of their authors as of the date of publication and do not necessarily reflect the official position of ALLATRA or any other public association, organization, project, partner, affiliated entity, or individual unless explicitly stated otherwise.

Publication of this material is intended to encourage open scientific dialogue and does not in itself constitute institutional endorsement, scientific confirmation, expert opinion, or professional medical advice.

Full Podcast Transcript

Dr. Lorne Hofseth

They are small enough to get inside of cells, in between cells, and so to get out of the bloodstream. These cancers have been showing up as very aggressive. Stay tuned, in the next 20 to 30 years, we'll start understanding the real link between the exposome and early onset carcinogenesis. And I'm going to put my, you know, my bet on microplastics being a key part of this rise in chronic diseases that we're seeing. Nanoplastics might be more harmful than microplastics, but our technology to detect nanoplastics is not there yet.

Narrator

Doctor Lorne Hofseth, Professor and Associate Dean for Research at the University of South Carolina College of Pharmacy and Director of the Center for Colon Cancer Research. His work focuses on the links between chronic inflammation, environmental exposures, diet, the microbiome, DNA damage, and colorectal cancer prevention.

Dr. Karolína Hronová

Welcome to the ALLATRA Global Research Center podcast. I'm joined today by co-host Doctor Jeffrey Long. Hello.

Dr. Jeffrey Long

Well, hello. Thank you so much. It's a real pleasure to be here. Big thanks to the organizers of producing this very important presentation. I'm Doctor Jeffrey Long. I'm a radiation oncology physician. I practice in rural Kentucky. I've spoken in the past about nanoplastics and microplastics and also have a special interest in colorectal cancer.

Dr. Karolína Hronová

My name is Karolina Hronova and I'm a clinical pharmacologist and a volunteer researcher at ALLATRA GRC. Today, we are honored to speak with Doctor Lorne J. Hofseth, professor and Associate Dean for Research at the University of South Carolina College of Pharmacy and Director of the Center for Colon Cancer Research. His work focuses on the links between chronic inflammation, environmental exposures, diet, the microbiome, DNA damage, and colorectal cancer prevention. Doctor Hofseth, we are happy to have you here with us.

Dr. Lorne Hofseth

I'm happy to be here. Thank you.

Dr. Karolína Hronová

We will explore a question that is becoming increasingly urgent. How do modern environmental and dietary exposures influence inflammation, cancer risk, and especially the rising burden of early-onset colorectal cancer? We will also discuss emerging concerns about micro and nanoplastics, what is known, what remains uncertain, and what kind of research is most needed now. Doctor Hofseth, before we begin, could you briefly share what you and your team are working on right now? What are the main questions currently driving your lab?

Dr. Lorne Hofseth

Sure. Well, for most of my career, I've focused on colorectal cancer and the causes of colorectal cancer and ways to prevent colorectal cancer and the mechanisms that lead to colorectal cancer. And one of those mechanisms is indeed inflammation. And so I guess what's been renting a space in my head over the last 5 to 10 years has been this rise in early-onset colorectal cancers. So, over the past 40 years or so, for a variety of reasons, we've gotten a handle and we've, there's been a reduction in the incidence and the death rate from colorectal in older people, people over 50 years old, But there's been a rise in early-onset colorectal cancer. And up until recently, we really haven't found out why.

And so these factors have to address those four factors, so again: have a temporal trend since the late 80s, have a global rise, kids have to be exposed, and it has to attack one of those mechanisms. And when you look at that, you look at the entirety of the literature, one that comes up is of course, microplastics. A SAD diet — a Standard American Diet, ultra-processed food diet. Other things that have been on the rise in the last 40 years include obesity, metabolic dysregulation, stress… Psychological stress has been on the rise And then we come to antibiotics and synthetic food dyes.

Dr. Jeffrey Long

Absolutely outstanding. We're going to explore in depth some of those very important and fascinating points that you just brought up. But just as an overview, could you tell us why you chose colorectal cancer as one of your main research focuses? Why colorectal cancer specifically? I mean, as you know, there's many cancers that are influenced by inflammation and environmental exposures. So for you, why did you choose colorectal cancer and how did that become the model for your scientific investigations?

Dr. Lorne Hofseth

Well, realistically, if you go back to my PhD, I was studying inflammation in bladder cancer. And in my second postdoc, I landed a postdoc with one of the most influential cancer scientists on the globe, and his name is Curtis Harris. And I worked under him at the NCI, and he was using just that… I was looking at models of inflammation and cancer, and he was using colorectal cancer as a model, carefully chosen and wisely chosen, because you can study the pathways and it's accessible. It has surrogate biomarkers like poop. And so it provides a good model for studying the link between inflammation and carcinogenesis.

Dr. Karolína Hronová

Okay. And for someone listening who is not a physician or a scientist, why should colorectal cancer be on the radar even before symptoms appear?

Dr. Lorne Hofseth

Well, if we're again, if we're talking about early-onset colorectal cancer, these cancers have been showing up as very aggressive and late. So, it should be on our radar. It's not only on the radar of people over 50, but don't confuse colorectal cancer symptoms with hemorrhoids. Or a menstrual cycle, you know, with actual colorectal cancer. So it's awareness not only as a physician but also as a young person. So we're trying to create that awareness as well.

Dr. Jeffrey Long

Well, thanks for those comments. You know, to me as a radiation oncology physician, the rise in early-onset colorectal cancer is especially alarming. Just this last week, I saw a 36-year-old metastatic rectal cancer. She's incurable. So I'm concerned about this, as are many, many other people. So diet, obesity, the microbiome disruption, environmental chemicals, antibiotics, sedentary lifestyle, stress, sleep disruption—all have been discussed as possible contributors. And you've already started talking about those. Of all these many factors, which of the known factors do you currently consider to be the most important and which factors are still uncertain?

Dr. Lorne Hofseth

Well, I don't think that there's a single cause. So… and there won't be a single cause. I think, these add up and are synergistic, and there's specific people that might be at risk. And people might be at risk at a certain time period of their lives. So whether children, developing children of course, are exposed to carcinogens, including all that list that you list. And I'm going to focus on synthetic food dyes and microplastics. And I'm actually more concerned with microplastics recently. And we'll talk about that later. But I do think that this change, this increase in colors and increase in ultra-processed foods that's been happening clearly over the last 40 years. You look at the 1960s and 70s: cereal aisles—they're all gray and brown. 80, well, 70s, 80s and 90s—a bunch of colors show up. So that is clearly happening. And then the data, the epidemiological data, like I said, that's coming out of Harvard and other groups is showing that this ultra-processed diet is causing harm. And I think it's the carcinogens that are in them.. by carcinogens I mean, you know, high levels of nitrosamines maybe, but also, you know, DNA damaging agents, inflammatory promoting agents causing… as I see it in my brain, a simmering inflammation. So, all these ingredients, all these fake ingredients that are in ultra-processed foods are causing simmering inflammation to the cells, to the body, to the DNA that causes mutations over time. If one consumes Standard American Diet over years, over decades as a dietary pattern, there's going to be accumulation of mutations, including cancer-driving mutations. And so that's how I see it. So I circle back to a Standard American Diet is a key driver of this. What's inside of it? Probably a bunch of things inside of it, including synthetic food dyes.

Dr. Karolína Hronová

You have already mentioned the contributors that have actually changed during time, possibly contributing to this early-onset colorectal cancer. Regarding the inflammation that you are studying, what led you to focus on this topic specifically? What was your motivation to study specifically inflammation as, let's say, one of the processes in pathophysiology?

Dr. Lorne Hofseth

Well, I circle back to my PhD from 1990 to 1996. I started studying [under] my supervisor at Simon Fraser University, doctor Miriam Rosin, who just recently retired but is still active. She was studying inflammation as a key driver of carcinogenesis, one of the few people that was doing so. So I got started to understand, hey, there's a lot of bad things in this inflammation. You know, it could be a key substrate of carcinogenesis, indeed. So I started studying it as a key driver of bladder cancer. And in patients with indwelling catheterizations, those with multiple sclerosis and quadriplegics, they tend to have catheterization for their lifetime, and they get a lot of infections that causes inflammation in the bladder. They have a high risk of bladder cancer, and I was studying that link. And then over time, as I studied it, since for the last 30 years, quite frankly, you know, people have recognized inflammation is not only a key substrate of carcinogenesis, but probably most chronic diseases, and so including cardiovascular disease, diabetes and Alzheimer's disease, many of these chronic diseases have a key substrate as inflammation happening. So to tame that is a critical method of treating or preventing these diseases.

Dr. Jeffrey Long

You know, you've made some very important points about inflammation and also about cancer. So for a general audience, how would you explain the pathway from chronic low-grade inflammation to DNA damage, abnormal cell behavior and ultimately cancer?

Dr. Lorne Hofseth

As I alluded to before, inflammation, there's a lot of bad things in inflammation, including reactive oxygen species. So let's imagine these free radicals that are attacking DNA, okay? So chronic inflammation, there's something that happened to that tissue. And chronic inflammation is happening to that tissue. Say, it was inflammatory bowel disease. Let's imagine ulcerative colitis. So there's a chronic inflammation that occurs with reactive oxygen species, free radicals. These are known, they will damage DNA. So if there's a chronic peppering of this DNA through inflammation, through reactive oxygen species, at one point there's probably going to be a mutation. And at another point there's probably going to be a mutation in a key cancer driver gene. Like if folks have heard of K-Ras or c-MYC, these are called oncogenes. And if you mutate those oncogenes, that changes a cell into controlled cell proliferation to uncontrolled cell proliferation. You can also mutate tumor suppressor genes. And so tumor suppressor genes actually stop cancer from happening. So if they're working properly, they're slowing, they're controlling cell division. So if you have the reactive oxygen species mutating a suppressor gene and stopping that from happening, cancer is going to become out of control cells, cellular division is going to become out of control. And there you have cancer.

Dr. Jeffrey Long

Very interesting. Thanks for that explanation. Your current research also seems to connect obesity, metabolic dysregulation, inflammation, the microbiome and connecting it with colorectal cancer risk. How do you see the relationship between metabolism and importantly colon cancer prevention?

Dr. Lorne Hofseth

Well, it does come down to diet and exercise and that will keep your metabolism healthy. But let's take obesity and what happens during abnormal metabolism, metabolic dysregulation: you start to get an accumulation of fat, of visceral fat, and you start to get insulin resistance. And associated with that insulin resistance and that visceral fat accumulation again, comes down to inflammation and inflammatory cytokines. There might be a reduction in some of the hormones that are associated… like adiponectin and an increase in cytokines. And so that will all perpetuate the metabolic dysregulation and perpetuate chronic disease. So…

Dr. Karolína Hronová

Oh, you know, I'm specifically interested because you mentioned that you have studied, or you are studying still, the food dyes, including Allura Red, Red 40. So what made you actually suspect about these possible contributors for colon health problems, and what have your findings until now shown up?

Dr. Lorne Hofseth

Okay. I'll try to keep this one short, I guess, because it could be a very long answer, but what got me interested? Well, they're petroleum-based dyes. Okay? So with this evidence that this Standard American Diet, the ultra-processed, colorful, fake-colored food is driving this increased risk in colorectal cancer, I started to look at the colors. And so the colors happened to be petroleum-based, meaning that, you know, it has the basic building blocks of petroleum, like benzene, and what is the other… toluene. So, some of these building blocks are used to make these synthetic food dyes, including Red 40, including Blue 1, including it, ended up being nine FDA approved synthetic food dyes. And so I started sprinkling them on cells and asking them whether they were causing DNA damage. And the answer was yes. And so I then had a PhD student start feeding some of the more common ones, Red 40 being the most common both in Europe and in the United States. And so we've had mice Red 40 at levels consistent with that consumed by humans for half their life—for nine months. And our hypothesis was that synthetic food dyes or Red 40 was going to cause colorectal cancer in these mice that were feeding them, they were fed nothing else, not a carcinogen, just Red 40 in the water bottles. And so at the end of the nine months, our results were in fact not consistent with the hypothesis. But what did happen? Again, I'm going back to this causing simmering inflammation. There was an increase in the inflammatory biomarkers in the distal colon of the mice that were consuming Red 40. And there was a dysbiosis. So it was that there was an interaction with the microbiome as well. And this is important, but we did not indeed find colorectal cancer happening. But I've been following this pathway of synthetic food dyes because I truly believe that they are bad for people and they're especially bad for kids, and we should get them out of our diet. But in the United States, it's very difficult to do that. You have to have, as I see it, three stars aligning. You have to have the science happening. And by science, I mean something called the Delaney Clause. The Delaney Clause was named after… I forget his first name, Delaney. He was a congressman from New York, and he had a clause that was attached to the 1938 Food and Drug and Cosmetic Act that says any food additive that causes cancer in humans or animals or animals can't be used in our food. And when that Clause came into place in, I believe, 1957, I want to say, or 1958, it knocked a bunch of food dyes out of the table. So that was a good thing. But since then we've had nine. And one recently has been knocked off and that's called Red 3. And the reason it was knocked off was because it triggered the Delaney Clause. But it didn't trigger the Delaney Clause lately, it triggered the Delaney Clause in 1989, I believe. Doctor Borzelleca in the University of Virginia fed mice.. no, rats. Rats, and this is important. Fed rats — because rats are particularly sensitive to synthetic food dyes, by the way — fed rats for their entire lifetime and found that the rats that were fed Red 3 had an increased thyroid cancers. And that officially triggered the Delaney Clause in 1989. But you need two other factors that need to come into play. You need public awareness and support through the public, and that will drive policy through our leaders, right?

And RFK Jr. Is particularly interested in synthetic food dyes, correct? And so that has to happen, whatever the politics is, that has to be supported at that level because it officially triggered the Delaney Clause in 1989, and it took, what, 40 or whatever, how many years, 30 to 40 years to actually get it out of our diet. So I've been focused on policy support. So those three factors in the end have to line up. So I've been focused on triggering the Delaney Clause with Red 40. I have not yet, but I intend to. And that's one thing I can do. But in the end to go from idea to discovery, guess what you have to have? Money. So I've still got to garner money to address the hypothesis that Red 40 causes colorectal cancer in a preclinical animal model. And if I show that, then that triggers the Delaney Clause, then I just have to get the public on board and the policy makers on board. So that's the Red 40 synthetic food dye story. And that continues. But unfortunately, until I get more funding, I can't continue some of these experiments. It is what it is.

Dr. Jeffrey Long

Well, I really want to thank you for that very detailed discussion. Food dyes are of relevance and, as you say, a concern to all of us. Going to another topic, as a radiation oncology physician, I serve a medically underserved area. I absolutely see societal disparities literally every day that I'm practicing. But you have also worked on colorectal cancer disparities. Tell us all about what kind of disparities. Why does this matter?

Dr. Lorne Hofseth

Well, we've been looking at disparities in colorectal cancer in both rural communities and in African Americans. And because in both cases, there's not only a higher incidence, but a higher risk of death from colorectal cancer. And so we are looking more at the biological side of, why is it a metabolic dysregulation driver? Is that driving it? So we're currently collecting samples from… we're currently carrying out an intervention trial where we're recruiting obese white folks and obese black folks. And we're splitting them into two groups. Either we're letting them continue doing what they're doing, or we put them on an intervention diet, an anti-inflammatory diet. Imagine a Mediterranean diet, a lot of fruits and vegetables, that type of diet. And so we're measuring insulin resistance and other biomarkers of cancer.

Dr. Karolína Hronová

Okay. In your 2026 review on microplastics early-onset carcinogenesis, you describe microplastics and nanoplastics as a possible emerging concern. You have already talked about it today while emphasizing that still the causality must be established, has not been established yet. So what is the strongest evidence today for the connection between micro- and nanoplastics and colorectal cancer and early-onset colorectal cancer, and what is still missing? If you can just go into deeper detail in that?

Dr. Lorne Hofseth

Well, there's more still missing than what's known. Okay, let's start at what's known in terms of preclinical and human evidence. Preclinical evidence says that if you feed... so folks have been feeding mice different types of microplastics and nanoplastics. And we gotta understand, there's many types of micro- and nanoplastics, and we're talking about microplastics. We're talking one micron and above and below five millimetres, actually. And then nanoplastics is under one micron. And the evidence and people seem to be agreeing that nanoplastics might be more harmful than microplastics. But our technology to detect nanoplastics is not there yet. And so that's one thing that people are working on is the detection of micro- and nanoplastics, not only in vitro, but especially in humans. But what we do know in terms of preclinical animal models is that if you feed mice microplastics, say polyethylene, these microplastics tend to accumulate in the colon, especially in mice that are given what's called dextran sodium sulfate. It's a detergent that's an animal model of colitis and colon cancer. So if they feed this DSS, it aggravates the colon, and they also feed them these microplastics. Whatever size they choose, whether it's five microns up to 100 microns, they feed them, and they seem to accumulate in the colon and cause inflammation in that colon. So there's some preclinical evidence, but there's way more that has to be done, including the types of microplastics. The most common ones are polyethylene, polyethylene terephthalate, which is the water bottles—the ones used for water bottles you see all the time—polystyrenes, which are styrofoam cups, polypropylene, PVC, nylon. And I think that's it. I might have mentioned six. Those are the most common. So, and we don't know. We don't know what size is the most important, whether it's the five micron, 100 micron, larger, or under one micron, which would be the nanoplastics. We don't know the main drivers there.

Dr. Karolína Hronová

Mhm.

Dr. Lorne Hofseth

Also, in terms of humans, only in 2019 was the first ever time we detected microplastics in humans, and that was in the poop. Since then, there's only been one, maybe a second study that has measured microplastics. Again, it's difficult to measure nanoplastics. We're not there with the technology yet. But the microplastics have been found in not only the poop, but the colon cancers compared to normal tissue that's right next to it. So there's a higher level of microplastics in the colorectal cancers. Also, though, since 2019, as you probably know, as you've probably heard, everybody that's measuring microplastics in humans has found them in almost 100% of the samples, unfortunately. And that includes the samples, you know, the brain, the breast, the breast milk, you know, all these things are being found. Microplastics are being found everywhere in our body. So again, 2019, that's the first time. So the alarm bells are sounding, and it seems like the scientists, hopefully, are stepping up not only for detection, improving detection, that'd be the engineers—but understanding where these things go, what type is the most hazardous, and what size might be the most hazardous, and to which disease. So all those questions, unfortunately, aren't known yet. And it's a global thing, right?

Dr. Karolína Hronová

Yeah.

Dr. Jeffrey Long

Oh, absolutely. Now, you've made some very important comments about how nanoplastics might contribute to carcinogenesis, but let's drill down on that very important issue. So mechanically, how exactly could microplastics or nanoplastics actually contribute to carcinogenesis? And are we talking about, say, particle induced inflammation, oxidative stress, adsorbed pollutants in the microplastics and nanoplastics, is that the additives in the plastics plastics themselves, microbiome effects? Or is it some combination of all of these mechanisms?

Dr. Lorne Hofseth

Let's go one at a time. It's a combination of all those mechanisms, for sure, but I envision it as... So it's a microplastic— by the way, it's an electrostatically charged microplastic, which is an important feature of it that's carrying a lot of other stuff, including forever chemicals, including endocrine disruptors and other things. So it's carrying all of that. All these things are foreign to your body. In other words, it's called a xenobiotic. Any xenobiotic—a virus, a bacteria, cigarette smoke, any synthetic food dyes—but especially microplastics because they're everywhere—is a xenobiotic. And a xenobiotic, if it lands in your body and it stays there, it's going to cause an immune reaction and inflammation, a slow-simmering inflammation that, again, over time will cause mutations and cause carcinogenesis. But again, circling back to which ones are important and what are the features of each that are important, we don't know yet. I suspect an interaction with the microbiome is going to be a driver as well. So I'm not sure whatever other mechanisms you mentioned, but every single one you mentioned, I would say yes, that microplastics and especially nanoplastics—those are the ones that I was... I was watching an NIH workshop. Actually, I'm not sure if you folks were on that call, but there was an NIH workshop that I could join by remote last Thursday and Friday. And I learned a lot.

And I learned that probably the consensus is the nanoplastics are more harmful. We don't know yet. We don't know yet, but that's probably the case because they are small enough to get inside of cells, in between cells, and so, to get out of the bloodstream. The viruses and the bacteria, I believe, are in between one nanometer and 200 nanometers. So those are the sizes that can get into your cells. So those are the sizes of nanoplastics. And those indeed are in our bodies. But until we can detect them in our bodies, you can't see them. And we can't see what they're doing to our bodies. But in the meantime, we can do preclinical trials. And I'm not sure if those questions have been answered. If you give a mouse a nanoplastic versus a microplastic, which one is causing more damage? And let's step back, I think the answer has been that this question has been answered somewhat in some labs. And the answer is the nanoplastics indeed get into cells, and they indeed drive the expression of pro-inflammatory markers like NF-kappa B or iNOS or COX-2. So you expose cells to nanoplastics versus microplastics. The nanoplastics will cause the expression of many of the inflammatory markers. But again, we don't know if that's happening in humans because we can't detect it yet.

Dr. Karolína Hronová

Yeah, definitely. Much research must be done in that field. You also mentioned that we already— still, the technology that we have today is not, let's say, perfect for detecting micro-, and not to talk about nanoplastics. So what do we need, actually? What, what do we need in that field specifically? You actually, what would help you in your research? Because you focus also on micro- and nanoplastics, and what kind of technology do you personally, would you personally appreciate?

Dr. Lorne Hofseth

To give you an understanding of the technology we have now…

Dr. Karolína Hronová

Yeah.] to study micro- and nanoplastics is a range from eyeball to microscopy. And more recently, we've been using confocal microscopy, which can look at the 3D structure of microplastics. But I say microplastics because it can't get down to the nanometer scale. When you go to the nanometer scale, you're looking at other mechanisms or other detection mechanisms, and that's mostly spectroscopy and what's called Raman spectroscopy and Fourier spectroscopy. And so, for example, this spectrometer can tell the difference between the types of microplastics, whether they're PE or polystyrene or polypropylene, etc. Well, let's look at the ARPA-H and what they're looking at.

Dr. Lorne Hofseth

] They're looking at better ways to detect microplastics, and especially in humans. Currently, our ways of detecting it are through microscopy. We're looking at confocal microscopy that looks at whether the microplastic is there just at the micron scale, not the nanoplastics scale, especially trying to look at it from in human tissues. So to start looking at a smaller scale, at the low-micron scale, you're looking at what's called spectroscopy—Raman spectroscopy and Fourier spectroscopy. These can detect lower levels, low-micron… to the one-micron scale of microplastics and tell the types. But then when you want to look at the nano scale and you want to look at that scale, right, it gets more difficult.

One discussion that's been happening in the circles of microplastics is flow cytometry. So flow cytometry is a technology that you can throw a bunch of cells through a column, and there'll be a bunch of lasers, and those bunch of lasers will be able to tell the type of cells that are thrown through that column. Well, we can easily do that. You can envision with some plasma that you've taken from somebody or urine and throw it through a flow cytometer, and it's going to have a bunch of lasers that's going to be able to detect microplastics and especially nanoplastics. And you could do that at scale. So I'm hoping that not only the whole entirety of the microplastic community and nanoplastic community can get to there, but I'm hoping that we can get there from our flow cytometry core that's just upstairs.

Dr. Karolína Hronová

Wow.

Dr. Lorne Hofseth

Yeah.

Dr. Jeffrey Long

Very, very good. You know, it's concerning to me, and I'm sure to pretty much every viewer here about how widespread microplastics and nanoplastics are in the environment, how much we're exposed to them. Here's a question: if exposure begins in utero or, say, in early childhood, could it contribute decades later to early onset cancer? And could you explain this to the general public how this possibility could be tested scientifically? Now, I know you've made some comments on that, but do you want to drill down on any additional comments you have on these important questions?

Dr. Lorne Hofseth

The ultimate experiment would be, you know, having over a million subjects and start collecting samples from mother in utero, and then from birth to adulthood and beyond. And so some of those studies are actually happening, but not at a perfect level because at a perfect level, you want to not only start collecting from mothers, but from babies every year biospecimens, biomonitors on these 1 million folks for a half a century. So for 50 years, following them ahead in time. So you're understanding the exposures, what's called the exposome, that the people are exposed to, not only mothers but babies, and then follow them up ahead in time and see if they get cancer or other chronic disease.

And then you use an AI technology of some kind. We're collaborating with an AI engineer, Pooyan Jamshidi. And he does what's called causal AI. So it's using, I look at it as bioinformatics on steroids. And so finding stronger links between the exposome and the outcome, which might be, in our case, we're looking at cancer, but any outcome. So yeah, you need a bunch of people. You need to follow them ahead of time from birth to adulthood. And you have to collect biospecimens along the way, poop, pee, saliva, and maybe take biopsies along the way as well and collaborate with engineers and AI scientists and see where those links are. Now, some databases are starting this. We've heard of the UK Biobank, you've heard of* All of Us*, those two, especially All of Us. I think they're aiming for over a million folks, and they've recently opened it up to recruitment of children in 2023 only. So you can imagine it's going to take us about 50 years to follow those folks ahead in time for 50 years. So, you know, we're certainly not there yet. We have to wait, because these large databases that actually collect samples and collect the right information, collect the food frequency questionnaires, have only started recently.

And that would be… there's a couple other ones. One is called HELIX. Uh, let me see, I got—oh, here. One is called HELIX. This is the Health and Environment for Children and Adolescents study. And this is out of the UK, and the goal of the study is to harmonize a study of mother-child pairs to discover how multiple environmental exposures affect growth, development, and health. And so they've recruited and are recruiting about 1,300 mother-child pairs. And they just started recruitment only ten years ago. So that study, there's also another study that I came across called the ECHO study. And this is out of the NIH, Environmental Influences on Child Health Outcomes. And they follow a diverse group of pregnant people and their children from before birth into childhood and into adolescence and maybe adulthood. And they have around 63,000 folks. So stay tuned for those studies that might garner some information on exposome-cancer link. But these very large human trials honestly are just starting up. So stay tuned, in the next 20 to 30 years, we'll start understanding the real link between the exposome and early-onset carcinogenesis. And I'm going to put my, you know, my bet on microplastics being a key part of this rise in chronic diseases that we're seeing.

Dr. Karolína Hronová

That pushes me to the question, actually, if you had the resources to launch one international research program on environmental exposures and early-onset cancer, what would you study first? You already described the concept of long term studies and so on. If you had the chance to launch something in that direction, what would that be?

Dr. Lorne Hofseth

Well, we just described it—it would be a very large, over 1 million people trial, multi-global trial. Because many of these only come out of the UK or only kind of come out of the United States or only come out of Finland. Finland also has a very good database, long-term database, but they didn't collect biospecimens along the way either. So, again, going back to the perfect experiment, you're getting a lot of people collecting a lot of samples at a high frequency and biomonitoring along the way for 50 years. How much would that cost? Got a guess?

Dr. Karolína Hronová

Well, maybe we need the results a little bit earlier than in 50 years.

Dr. Lorne Hofseth

But that would be the perfect experiment. Now, to do that faster, you look at preclinical animal models.

Dr. Karolína Hronová

Yes, exactly.

Dr. Lorne Hofseth

And we can look at mechanism. But yes, that would be the perfect experiment, following ahead in time and seeing what diseases arise from those exposures that happened long ago.

Dr. Jeffrey Long

Very good. You know, it's heartening to me that there is some efforts being put into doing research, even if we're going to find the results decades from now. But let's drill down on that. Looking into the future of cancer research more broadly, and with a focus on your expertise in colorectal cancer, so with the rapid development of molecular biology, immunotherapy, precision medicine, early detection technologies, and now, of course, artificial intelligence, how do you see the field evolving over the next 10 to 20 years? Do you think humanity has a realistic chance not only to treat cancer more effectively, but to one day to prevent or even eliminate many forms of cancer as a major cause of death?

Dr. Lorne Hofseth

One of the biggest breakthroughs, in my opinion, for cancer treatment, of course, is immunotherapy and especially the immune checkpoint inhibitors. Those are amazing drugs that work amazingly in certain populations, especially those with what's called microsatellite instability-high patients. So that's a big breakthrough. I have a lot of hope that it will make a lot of progress in the next 20 years, but I don't think we'll eliminate that many cancers unless we find what they call a magic bullet for a specific type of cancer. But that's unlikely. I hope there's going to be a lot more progress in, and probably, there's going to be more progress in immunotherapy than small molecules, in my opinion, too. And so the biggest hope is immunotherapy. And I'll end this answer with a personal story. My mom had what's called Merkel cell carcinoma in 2018. And she lives in Canada. I come from Canada, and specifically Vancouver, Canada. And she lives in Victoria, Canada. So she came down with what's called Merkel cell carcinoma. It's a form of melanoma. It's, but it's different and it's very deadly. And she had stage 4 Merkel cell carcinoma and she was in a bad state. And it turns out that immune checkpoint inhibitors were approved for Merkel cell carcinoma in the United States six months earlier. So her physician contacted the FDA and asked for the drug for compassionate purposes, and she got it. And make a long story short, she's alive today and she's very healthy. And those drugs worked amazingly for my mom, who otherwise probably wouldn't be with us. And that's a great story about these immune checkpoint inhibitors. And I think they've saved a lot of lives. And I think we'll continue to find out more on immunotherapy. And that's, that's as I see it, our biggest hope.

Dr. Jeffrey Long

Thank you so much for sharing that really inspirational story about your mother. I can tell you, in the clinic, immunotherapy has been a complete game changer. We are curing more cancers than ever was ever possible before because of immunotherapy and some of those major breakthroughs. And for your mother to have stage 4 Merkel cell you're right. Very aggressive. I mean, that would have been considered a death sentence in that era. And yet, wow, here she is alive today. What an inspiring way to wrap up this discussion here!

Dr. Lorne Hofseth

Awesome.

Dr. Karolína Hronová

Thank you very much for this insightful conversation. Doctor Hofseth, would you like to make some final words? Give some final words to our viewers, some message at the end of our conversation?

Dr. Lorne Hofseth

I'll end up with a message about microplastics. I think these microplastics are dangerous. They're, I think, a threat to global health, chronic diseases. And I think that scientists and policymakers have to get their heads around this as a big problem. And everybody has to work together, scientists and policymakers and the public, to reduce this problem. And as I see it, chemists got us into this problem, Leo Baekeland back in 1907. So I think chemists might be able to get us out of this problem. So, for example, well, actually, chemists and biologists might be able to get us out of this problem. And I say that because chemists can find a way to find the chemistry to break down the polymers to monomers. And so I think that's happening in the chemistry world. So you can envision a big dump truck of one-use water bottles and then pour a dump truck of the solution that breaks down these water bottles, make them into monomers, and that can be easily broken down naturally. So that's one way we might be able to address this problem. Another way is to work with the molecular biologists. And we can overexpress enzymes, enzymes that might break down plastics. There's one enzyme called polyethylene hydroxylase, and we can overexpress this and expose plastics to this bacteria that's overexpressing it. And it actually breaks down the bacteria. So you can envision, again, a dump truck full of one-use water bottles and pouring a dump truck of overexpressing E. coli bacteria overexpressing the polyethylene hydroxylase and those naturally breaking down the plastics. So those are two ways we might be able to address the problem. But we've really got to wrap our heads around the problem itself, how big is the problem? And my head's exploding too, because the answer is the problem's huge.

Dr. Jeffrey Long

This has been an outstanding discussion covering a great deal of topics. What is obvious is that what we don't know about nanoplastics and microplastics far exceeds what we do know. These are topics—microplastics and nanoplastics—that affect everybody. It's literally in everyone's tissue globally. So this is certainly, this presentation today is a plea for more research, more focus on helping us all in the future to learn a lot more about nanoplastics and microplastics, and how they impact cancer production and how they impact other health care issues.

Dr. Karolína Hronová

At ALLATRA Global Research Center, we believe that science has a crucial role in protecting human health and the future of our society. Conversations like this help build a bridge between researchers, physicians, policymakers, and the public. Thank you, Doctor Hofseth, for sharing your expertise and your perspective. Thank you also to my co-host, Doctor Jeffrey Long.

Dr. Jeffrey Long

Oh, thank you very much. This was an outstanding video. Certainly this is going to be both informative and to some extent inspirational to a huge number of people. Thank you all to ALLATRA and everyone that had a part in producing this.

Dr. Karolína Hronová

Thank you for watching.