Why are cancer rates rising among younger people? – with Kimmie Ng and Charles Swanton

Jennifer Dixon:

Surprisingly, the incidence of cancer is rising in the under-50s and in high-income countries. A string of international studies has reported this trend, which began to uptick in the early 1990s. And there are lots of theories as to why; some to do with risk factors and some to do with wider environmental exposures that affect all of us. So what exactly is going on and what to do about it? 

Well, with me to discuss all this, I'm delighted to have two guests: Dr Kimmie Ng, who is specialist in oncology at the Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School in Boston. And Dr Charles Swanson, who is deputy clinical Director at Francis Crick Institute and Chief Clinician at Cancer Research UK. He's also an NHS consultant oncologist at UCLH. Welcome, both.

Everyone who's been seeing some of the recent studies in the last couple of years about the rising incidence in cancer among younger people, that is those under 50, must be feeling a bit concerned. In particular the rising incidence in successive cohorts. And I wonder if you both in your own words, could just chart the main headlines of the findings to date as you understand them, what we know about the cancers involved, the people involved and the strength of the studies?

Kimmie Ng:

So, there is a silver lining here, at least with regards to colorectal cancer, which is my area of research focus in that overall over the decades, the incidence of colorectal cancer and mortality related to colorectal cancer has been steadily declining. And this is largely attributed to improvements in screening and compliance with screening, as well as improvements in treatment. But what is disturbing is that these benefits and these improvements have been limited to people over the age of 50. And in younger individuals under the age of 50, there are dramatically different trends that we're seeing. Mainly that colorectal cancer incidence has increased by a steady 2% to 3% per year in these young people ever since the mid-1990s.

And this seems to be a global phenomenon. It does seem to be most pronounced in higher socioeconomic status countries. It does seem to be steepest among non-Hispanic whites, but it is affecting every race and ethnicity for which we have data. And so, this is certainly concerning because most of these patients actually do not have a genetic reason to be developing cancer early or oftentimes not even any risk factors for developing these cancers. So that is the big question. Why are these trends happening in young people?

Jennifer Dixon:

Charles, what would you add there?

Charles Swanton:

I think the first thing to say is that cancers under the age of 50 still account for a minority of all cancer diagnoses. Cancer Research UK estimates that around 10% of all cancer diagnoses occur below the age of 50, so I think one has a perspective on this. But despite that, as Kimmie rightly says, the incidence of a colorectal cancer example is on the rise in the under-50 age group. Cancer Research UK figures estimate about a 24% increase in incidence over the last 24 or so years, so I think between 2019 and 24 years before that.

So there is absolutely a noticeable rise. We see this in our clinical practice. We've had many discussions about young onset colorectal cancers that anecdotally are becoming more common in our clinical work, and that's borne out by the statistics. But it's not just colorectal cancer. I think it's important to say there are several other cancer types that are also on the rise in the under-50s, eight of which are cancers of the digestive system.

Of course, the multi-million dollar question is what's the reason for all of this? And I think that's part of the reason why Cancer Research UK and the NCI funded a Cancer Grand Challenge in this space to address that big question. But I think what we will almost certainly gather from research like this and others is that there's probably no one single cause that would explain all of these early onset cancer types.

Jennifer Dixon:

So, we talk about the under-50s, are we talking about adults under-50 or are we also talking about children zero to 18?

Charles Swanton:

I'm predominantly talking about adults.

Kimmie Ng:

What we do know, though, is that the rate of increase does seem to be steepest among the very youngest of those under-50. So for example, those individuals in their 20s have a steeper rate of increase of colorectal cancer than those in their 30s and 40s. And just anecdotally in my own clinic, unfortunately I have been seeing more children with colorectal cancer than I ever have before. So, although there isn't published data necessarily on the rate of increase and whether it's affecting the paediatric population, at least anecdotally I have certainly been seeing some children with colorectal cancer.

Charles Swanton:

Do you think that this relates to this birth cohort effect that Dr. Ogino and Dr. Ugai from Harvard have been discussing, where each successive generation has a higher risk of early onset cancer than the one before?

Kimmie Ng:

I absolutely do think it is related to the birth cohort effect. The published literature has not looked, I don't think, as young as the paediatric population. But I imagine if there is a birth cohort effect among other generations that it might certainly be affecting this youngest generation as well. There have been recent studies that do document that patients born in generation X have significantly higher rates of cancer than those born in the baby boomer generation. So it is quite disturbing that we are now seeing this in children.

Charles Swanton:

Many pundits and scientists, investigators mention obesity as one of the sort of possible risk factors for early onset colorectal cancer and cancer of the digestive system. My impression at least clinically is that that doesn't always bear fruit, that argument, and that many of these early onset cancers are associated with individuals who aren't obese or overweight.

Kimmie Ng:

Charles, I completely agree with you. In my own clinical experience and that of my colleagues, most of these young patients are not obese. They actually follow very healthy lifestyles. Many are triathletes and marathon runners, and so it is really puzzling why this is happening. I mean, the hypothesis put out there is that the reason why the incidence is rising among all digestive system cancers is this common theme of obesity being a risk factor. But again, I'm with you. I have not seen that myself in the patients whom I've taken care of.

Jennifer Dixon:

And you mentioned the digestive system, but there are some other cancers aren't there that are also on the rise in this age group?

Charles Swanton:

Well, I think breast cancer is an instructive one here because here I strongly suspect, and I think the literature bears this out, the reproductive issues are an underlying cause of the rise in breast cancer in younger age groups. We know for example, that parity is protective against breast cancer. And of course-

Jennifer Dixon:

That's the number of children people have just for non-medical listeners.

Charles Swanton:

That's right, sorry. And we're choosing to have children later on in our adult lives and fewer children. And that can be one of the reasons, for example, cancers that, carcinomas of the breast are rising in incidence in the younger age group. So again, this points the issue that Kimmie and I have just mentioned, that there's not going to be one single factor responsible for these early onset colorectal cancers that we're seeing.

Kimmie Ng:

A couple of other cancers that are rising as well that bear mention, thyroid cancer has also been increasing, although there may be a detection bias there where a lot of people are getting thyroid cancers incidentally discovered when they're getting scanned or evaluated for other reasons. And then, kidney cancer is also rising among the young. And so, again, it really is various cancer types that this is affecting.

Jennifer Dixon:

So, you began to talk about obesity as a possible hypothesis, but obviously not all the story. And considering the variety of cancers that are increasing in this age group, you wouldn't expect one particular causative factor. But what other hypotheses are around that you think are plausible?

Kimmie Ng:

We do think it's probably something in the environment, whether it's related to diet, whether it's related to lifestyle, whether it's something, again, just in the external world that we're living in. Because of this birth cohort effect that we're seeing where it really affects generations, we do think it's related to some recent environmental exposure. We also believe that these environmental exposures are likely acting over a lifetime. And so, it's exposures probably in early life, perhaps even as early as when someone is in utero or in infancy that are perhaps leading to an increased susceptibility to cancer down the road when they're young adults.

But what exactly those combination of factors are is still under active investigation. But there probably are some things related to diet with our increase in processed foods and just the quality of our diets declining over the generations that may be contributing. But it also could be something in our air or in the chemicals that we're exposed to on a daily basis, and so all of those things are being investigated.

Charles Swanton:

We are beginning to understand much more about how cancers are initiated and what has been clear, for example, is that there is more to cancer than simply the acquisition of mutations over time. For example, 5 to 10 years ago, the prevalent view was that carcinogens caused cancer by generating mutations. But now we've been made aware by groups like Allan Balmain and others that the cancer initiation process is complex and it requires both mutations to be pre-existing in the stem cell of origin of the cancer, but also in inflammatory stimulus, the so-called promoter that promotes the outgrowth the cells with mutations in.

And it's also become apparent that many carcinogens induce cancer without inducing DNA mutations. And that's a critical observation because in the past UV light, tobacco smoke, we know these carcinogens cause mutations, and it was thought and still is thought that's the dominant mechanism through which they induce cancer and all carcinogens would be like that. Work from the Prominent and Mutographs team led by Mike Stratton and Allan Balmain has shown very clearly that that's not the case. In fact, the majority of carcinogens induce cancer without driving DNA mutations possibly through inflammatory effects.

And the worry of course there is we lack the assays to really be able to understand the carcinogenic potential of new chemical matter that's introduced into our environments, as Kimmie's been alluding to, over the last three to four consecutive generations. We simply don't understand the mechanisms through which environmental exposures generate that inflammatory process that trigger the first cancer cell to initiate.

Jennifer Dixon:

I mean, there's quite a big literature on inflammation isn't there? And this business about allostatic load and biological ageing, which is fascinating. In fact, we had a podcast on it quite a while ago.

Charles Swanton:

Well, this is not new, of course. Our immunology colleagues have been telling us for three or four decades of the important role of chronic inflammation in cancer initiation. But it's only, I guess over the last 5 to 10 years that we've had the tools to really tease apart how inflammation triggers that first cancer initiation step.

Jennifer Dixon:

And could it be that there's an early exposure of some of these carcinogens? Or is it more likely do you think, to be a cumulative exposure?

Kimmie Ng:

I do think it's probably both. It's probably both early exposure, which then leads to cumulative exposure likely over a person's lifetime and early life and adolescence. Another very important potential contributor to inflammation and other processes that may lead to cancer and particularly colorectal cancer is the microbiome. And we do know that all of these environmental exposures, diet, lifestyle, the things in our air, can actually influence and change the shape of our microbiome, which then can have huge influence on our overall immune systems, and that of course is important in trying to fend off cancer. And so, a lot of research is also directed towards how is the composition of the microbiome perhaps contributing to this rise in young onset cancers?

Jennifer Dixon:

Given all these possible external environmental exposures, like forever chemicals or microplastics, why is it that the digestive system seems to be most affected if inflammation affects most cells from some of these exposures?

Charles Swanton:

Your point about why digestive cancers I think speaks to what this environmental trigger might be, gives us clues at least where to look. Kimmie will know much more about this than me, but we've had more than a passing interest in microplastics, and there are some very worrying statistics on just how much the burden or load of microplastics has increased through our diets over the last 20 to 25 years. And of course these are agents that cannot be degraded and accumulate, and as a result we are exposed to more and more on a successive generational basis.

And we know next to nothing about the interaction of microplastics with our bodies. There was a paper in New England Journal about some 4 to 6 months ago showing that microplastics contained in atheroma, which is furring of the blood vessels, predicted essentially risk of myocardial infarction and plaque rupture. So, we know these microplastics are already having a systemic effect in the context of cardiovascular biology, and I think many groups are beginning to look at this in the context of whether they may have cancer-initiating properties.

Kimmie Ng:

Microplastics is certainly an area of interest, but it is a difficult thing to study right now. We don't even necessarily know what the best assay is to measure microplastics, what compartment do we best measure it in that's clinically relevant? Is it the blood, is it tissue, is it stool? But certainly there is evidence that microplastics may be involved.

And it is interesting that the majority of cancers that are rising in young people are in the digestive system because that is one of the largest organ systems that does come into direct contact with the external world. And so it really, I think, just lends further support to the association and the likely contributor to this rising young onset cancer being something in the environment. We are looking at things like PFAS and pesticides and all of these things are so increasingly prevalent in the foods that we ingest that they probably are also playing a role. But as Charles mentioned before, it's not likely going to be one single exposure.

Jennifer Dixon:

Now, I can see that both of you are very serious researchers in the lab, say, let's put it that way, or on clinical research. But if you look at the other end of the telescope and you look at epidemiologists that are trying to figure out single factors, looking at large data sets, we've now got a lot of increases in computing power, linked data sets and AI. Do you think that that is a useful way to start looking at mass causative factors, seeing signals in the noise if you like? And if you do, is anyone doing any really go-ahead work in this area that you can identify?

Kimmie Ng:

I think AI has tremendous potential in helping us to answer a lot of the questions related to why young onset cancers may be rising. Given the discussion we've already had about how complex this is with the interaction of the environment or the exposome, which is everything that we're exposed to in the external environment with our immune systems, with the microbiome, with genomics, that's a huge amount of data to go through and to try to identify connections between, and so I think that's where AI has huge potential to help us with that.

The other area, and we are working on this, is whether we can leverage the huge amounts of data in electronic health records to really be able to pinpoint: are there signals or variables that may predict a higher risk of young onset cancer developing in people? And can we use that technology to identify patterns that may not already have pre-existing hypotheses to really help us understand how we can maybe identify these people early on and help with early detection and prevention?

Charles Swanton:

The power of AI here is to be able to see signals and patterns in data across scale. And when you've got clinical metadata combined with genomics, exposome data, lifestyle data, data across multiple different domains in multiple different countries and epidemiological studies, the power of AI I think is largely untapped I think when it comes to finding signals amongst all of the noise.

However, I think it's important to say that, yes, these AI and large language models may help us identify signals in the noise, but the fact is it will still mandate validation and functional analysis in laboratory systems. And that's I think quite challenging for many, many reasons, not least of all, there aren't, I would say, optimal models of tumour initiation that are readily available to scientists that mimic tumour initiation in humans. We have obviously rodent models, predominantly mouse models, but mice have a lifespan of 18 months and the tumours that we initiate in them in experimental systems in the lab initiate in somewhere between a month and 6 months. Whereas most human cancers, as we've heard from Kimmie, will evolve over a lifetime, and our lifetimes are 20 to 30 times longer than a mouse.

And so, really trying to mimic not just the exposome, but the temporal patterns of evolution in animal models is very, very difficult indeed. So proving cause and effect here is not a trivial undertaking.

Jennifer Dixon:

But presumably you've got a clutch of information and scientific inquiry in, let's call it, the lab end of the spectrum, albeit limited in some ways as you described there, Charlie. And you've also got this potential other domain which is this epidemiological set. Where's the best in class of that kind of epidemiological approach? Does it exist yet?

Charles Swanton:

This is exactly where the Cancer Grand Challenge initiative shines. And then why we funded Kimmie's group is because they brought together epidemiology with cancer prevention and functional biology to try to do exactly that. So to answer your question, there is no single group that can do this, which is why you need to be able to shift money across international borders to allow scientists like Kimmie and others to work together across states in the US, across countries internationally to bring these cohorts together to address this fundamental question.

Kimmie Ng:

I mean, it is so important to study this on a global scale. The rates of rise are different in different parts of the world. The rates of rise are different across races and ethnicities. And to really understand the underlying etiologies, you do need a global study population with comprehensive collection of exposome data, and comprehensive collection of biospecimens and maybe even serially through time to really try to get to the bottom of this. And we are now working to build these cohorts and these specimen banks across multiple different countries of young onset colorectal cancer patients. And epidemiology studies are very powerful.

But as Charles alluded to, we really need to understand the mechanism of action of some of these factors that are identified in these epidemiologic studies. And so, although models are not perfect, it would be valuable to use them to understand what stage of the life course are you most susceptible to some of these exposures? When is it acting most to influence the subsequent risk of cancer in young adulthood? And that's where model systems like mouse models may be very useful with their shorter lifespan.

Jennifer Dixon:

So, you mentioned ethnic differences, Kimmie, and I wondered if you could say something about socioeconomic differences?

Kimmie Ng:

We don't quite understand these trends that we're seeing, but what we do know is that the rates of rise do seem to be steepest in more Westernised societies with Westernised lifestyles and higher socioeconomic status. And they're probably somewhat related, but overall we know that there are disparities in the incidence and mortality of colorectal cancer by race and ethnicity, where Blacks are 20% more likely to develop colorectal cancer and when they do it's at a younger age, and 40% more likely to die of colorectal cancer than non-Hispanic whites.

But because the rates of rise do seem to be steepest among non-Hispanic whites, some of those disparities particularly for rectal cancer, which is the predominant type of colorectal cancer in young people, are actually narrowing because of this rise in young onset rectal cancer. I do think some of those risk factor differences among the different populations as well as inequities to access to quality care or quality screening probably are underlying this, but it's a very, very complex thing to study.

Jennifer Dixon:

There's a left-field question I've got here. If you see rising trends in early onset cancers, are there any other diseases that seem to be rising in incidents among younger people that could also be perhaps linked to inflammation?

Kimmie Ng:

Yeah, I mean I think we've alluded to obesity already, and there certainly has been a parallel rise in obesity rates, particularly among younger people over the same time period that has led to young onset cancers rising. But again, we've already discussed how the data around that are not necessarily completely consistent. We do know that conditions like diabetes and nonalcoholic steatohepatitis or fatty liver may also influence risk of cancers down the road. And those conditions are also increasing in young individuals, especially in younger generations like millennials and generation X. And so, we are certainly worried about the rise in these chronic conditions and whether they may be contributing somewhat to the rise in young onset cancer.

Charles Swanton:

Maybe I could add to that and just a couple of other things that have cropped up but we have had time to speak about in detail, which include antibiotic use, which has obviously changed quite considerably over the last 70 years. Inflammatory bowel disease is on the rise in adolescents since the 1980s, and that is obviously an established risk factor for colorectal cancer. Again, I don't think that's an overriding contributor to the early onset rise in colorectal cancer we're seeing. Kimmie is the expert, she'll be able to elaborate.

And then I think something we haven't touched upon in detail, but we briefly mentioned is the microbiome and how potentially the microbiome might have changed over the course of the last 70 years. And there is data emerging from the Cancer Grand Challenge groups showing that PKS-positive E. coli can induce mutations in endothelial cells of the gut that might in turn contribute to at least some of the cancer initiation processes. But that is obviously work in progress and I think still needs to be formally proven. Kimmie, what do you think?

Kimmie Ng:

I completely agree. That finding is really provocative and very interesting, and I think the evidence points to PKS-positive E. coli causing this mutational signature being a very early event in somebody's life, and again, consistent with our hypotheses that whatever exposure or inciting factor is happening is probably happening in the early life course.

Jennifer Dixon:

So, you mentioned the Grand Challenges, both of you. So here's a space to be able to just chart what are the frontiers now in trying to make progress on understanding this, but also to develop treatments?

Kimmie Ng:

The Cancer Research UK Grand Challenge programme has been absolutely transformative in allowing us to be able to make inroads into our understanding of the microbiome, particularly in young onset colorectal cancer. And I think the unique thing about this mechanism is that it can bring global groups together where it would be very hard to work together otherwise. And the value of that is not just bringing medical oncologists together, researchers, but a multidisciplinary team of people. And I think Charles alluded to, it's important to have all kinds of disciplines working on this. Epidemiologists, basic lab scientists, clinical researchers, people who can translate findings that we may discover in the epidemiologic space or the laboratory space into bedside interventions for patients in the forms of clinical trials.

And I think what we've come to understand is that in our optimistic team, the microbiome does seem to be important in responses to treatment as well, as there's evidence that organisms in our microbiome may actually be metabolising some of the chemotherapy drugs that we are giving to patients. It may also be metabolising them in such a way that affects side effects and toxicity to these treatments also. And there's probably a huge role of the microbiome in whether somebody responds to immunotherapy or not. These new class of immunotherapy drugs have been very disappointing in patients with colorectal cancer, and I think one of the main reasons may be the presence of the microbiome in the colon. And so, being able to tease that out in the context of this CRUK Grand Challenge grant has really been transformational.

Charles Swanton:

I think it's an extremely exciting time in the study of human biology, and we've discussed many of the reasons. I think you need a permissive grant funding environment, you need the tools and you need the data. And I think we're at that really fascinating crossroads where all of these opportunities now exist. We, for the first time, I think, are seeing over the last 5 to 10 years epidemiologists work with functional cell and animal biologists to try to bring causative, functional consequence to epidemiological observations. And epidemiology can only ever show associations, but the crucial thing is to link epidemiologists up with high-quality bench scientists and bioinformaticians to be able to really tease apart the underlying basis for these observations that, in turn, we hope will lead to the identification of new drug targets, public health strategies, prevention strategies, etc, that will unravel the biological basis of the diseases we're studying.

Jennifer Dixon:

In terms of what's around at the moment in terms of treatment frontiers, I noticed there's a piece in the papers today about ‘cancer vaccines’, as they're called in lay terms, and obviously there's been some progress, hasn't there? Immunotherapy for late stage melanoma in particular. But where are the late stage three trials? What might the public be seeing soon or are they not going to see anything soon?

Kimmie Ng:

Well, as it relates to young onset cancer, there currently are not any specific tailored treatments particularly for young people right now because it goes down to the question we don't really know yet what's different about cancers that arise in young people compared to older people. So, as the research advances and we discover unique molecular features, or other microbiome features specific to young onset cancers, we may indeed be able to develop some tailored and personalised treatments specifically for young people.

What we do know, unfortunately, is that the youngest patients do not seem to have longer or better survival compared to older patients. It might be that their cancers are less responsive to treatment. It might be unique molecular differences as yet to be uncovered, but it is quite distressing that younger people actually do not live longer. Despite being healthier and being able to receive higher doses and more cycles of chemotherapy, they don't actually have a longer survival.

Charles Swanton:

For me, the great opportunities here overlooked, I think it's fair to say partly because there's no commercial model for it is in cancer prevention. It's really only by understanding how tumours are initiated through these environmental exposures that we've been discussing today that will, combined with the functional biology that Kimmie and others are undertaking, that we're going to be able to identify new targets that we could potentially either modify people's diets or even offer one day, 20, 30, 40 years from now, perhaps a daily tablet to dampen down the inflammatory process to the extent which reduces the risk of early onset cancers.

If, for example, the cause the underlying exposome turns out to be something that we just can't address through dietary modification, let's say for example, it is microplastics, well, obviously reducing microplastic load from the diet is going to be a very difficult task. So, in the meantime, we would need to think about perhaps 20, 30 years from now, and of course this is all conjecture, so take it with a pinch of salt, an anti-inflammatory of some sort or another, perhaps like aspirin, that could dampen down the inflammatory system sufficiently to prevent the onset of cancer, but not too much that renders you at risk of infection, for example.

And there are examples of this. Lung cancer, my field, there's a drug called canakinumab, an anti-IL-1-beta antibody that through cardiovascular prevention trials has been shown to reduce the risk of incident new lung cancer primaries. So we know that anti-inflammatories can work. The key thing is establishing a commercial model so that pharmaceutical companies can see some route to reimbursement for their research and development costs. In cardiovascular medicine, we use statins all the time to reduce the risk of cardiovascular disease, but we don't really have a clear route to prevention other than tamoxifen and astrozole or aspirin in solid tumour oncology.

Kimmie Ng:

The other very important part of developing a chemo-preventive agent is the toxicity profile. We know that tamoxifen and other things may not necessarily have 100% uptake because of the toxicity profile. So, whatever agent we develop needs to also be very well tolerated over a period of decades for people to actually be compliant.

Jennifer Dixon:

For those people who are listening or to the general public who are living quite healthily, don't smoke, don't drink, aren't obese or moderately obese, is there anything you think at the moment they could do to mitigate any future risks of inflammatory related early onset cancer?

Kimmie Ng:

We do think that continuing to follow those healthy diet and lifestyle behaviour is still very important to protect against the risk of developing cancer. We also have been trying to undertake a public effort to raise awareness of colorectal cancer in particular, and that this could happen in a young person without a family history or genetic syndrome. It is amazing how many young people have never heard of colorectal cancer until they get diagnosed or really think it's something that could only happen to an older person. So, being aware and attuned to symptoms that may develop and seeking prompt medical attention for them is also very important towards early detection and hopefully improved outcomes.

And then I think public health efforts to really promote healthy lifestyles and diets starting in early childhood will be really important as, again, we do think it's a period of the lifetime of exposure to these factors that is likely meaningful.

Charles Swanton:

This is a really, really crucial question, actually. I think about it a lot. With my cancer research UK Chief Clinician hat on, the one thing I want to say more than anything is one has to profile the risks that we already know exist associated with, for example, tobacco smoke, UV light exposure, obesity, red meat, diet, etc. And then ask oneself the question: how do those risks stack up against each other?

And I think the important thing here to say is that the greatest risk factor for cancer across the board is tobacco smoke exposure. If you're a heavy smoker, you're a 15 to 30-fold, increased risk of lung cancer. One modifiable factor above all else I think first, second, and third is to stop smoking. That overwhelmingly is one of the greatest risk factors for cancer. And then when you are looking at obesity, red meat, diet, etc, the risks are there and they're real, and they come through multiple epidemiological studies, but they are considerably less than tobacco exposure. They're very significant at the population level, but at the individual level, the level of risk is lower. That doesn't mean you shouldn't try to modify it, but if I was going to pick one modifiable risk factor to tackle above all else, it would be tobacco smoke exposure.

Kimmie Ng:

I completely agree. It's a huge risk factor for multiple different types of cancers. Although obesity is not definitively linked to young onset cancer, I do think trying to combat the obesity challenge is also very important. But I think what all this really gets to is that it is so important, Charles, as you said, to identify who is at high risk for these young onset cancers. We know screening works. Screening decreases the incidence and mortality of cancer, but we can't screen everybody in the population. And so, if we can risk stratify and identify those people who have the high risk factors and identify them for earlier screening, that could certainly make a huge difference in decreasing the incidence of these young onset cancers.

Jennifer Dixon:

You're both cancer specialists, you know the field, the finger is pointing to some exposure agent or set of agents possibly to do with eating or drinking it sounds like, from what I've understood. We have a system of regulating food and water in this country and beverages. Do we have enough evidence at the moment to change any tack with respect to the level or intensity regulation that we now have on some of these chemicals, plastics, other things to do with food and drink? Do you know if the cancer community is having conversations with the regulators at all at this stage? Or is it far too early?

Kimmie Ng:

I think for some of these chemicals it may be far too early. And I'm by no means an expert in this area. In the United States at least, though, there had been efforts to try to improve diet quality in children and elementary school age children in particular, where they are really limiting the availability of, for example, sugar-sweetened beverages. So, I think those initial efforts are already underway to try to improve diet quality, to increase physical activity in the very young, all of which could decrease incidents further later in adulthood. But I'd be curious to hear what Charles thinks. I wonder if it's too early for some of these other chemicals.

Charles Swanton:

I think that's certainly my view right now. I think we do what we can to address the underlying cancer risk factors that we've discussed today. Healthy diet, exercise, obviously I've said it before, I'll say it, don't smoke, address obesity and overweight. And I think as regards water quality, etc, I think it will have to wait before we start to suggest modifiable factors because we simply don't know what the underlying biology is and how these early colorectal cancers and early cancers in general are initiated for the most part.

So, I think we just have to wait for grants like the Cancer Grand Challenge and Kimmie's team to read out on their phenomenal task, which is they're looking at 10 million individuals across the world and they're trying to tease apart biological factors from those 10 million individuals. It's a Herculean task this, and we'll just have to be patient before public health measures read out.

Jennifer Dixon:

And just last question, I guess, putting you both on the spot, where are you most hopeful given this agenda?

Kimmie Ng:

That's a hard question. I mean, I am very hopeful and I do think that the field of advances and understanding of why this is happening will be greatly accelerated by the CRUK Cancer Grand Challenge programme. I really hope that all of the multidisciplinary team science that is doing its important work will really lead to us being able to identify particularly individuals at high risk. Because as Charles said, I do think cancer prevention is the way to really make a dent in these incidents and mortality curves. And so, until we know what the causative factors are, or at least be able to identify higher risk people who may be eligible for earlier screening, I do think that's where I hope to see us in the next few years.

Charles Swanton:

I'm excited about essentially team multidisciplinary science. I mean, I don't think team science is the answer to everything, but I do think team science is particularly well suited to challenges like this. And essentially what it's doing is opening up a field that I call functional epidemiology or molecular cancer prevention. It's this cross-disciplinary interaction that brings function to observation. And that's really, I think, where the breakthroughs are going to be made. It's groups like Kimmie's and others that work together across boundaries and across specialties to really uncover very important human biology that will, I hope, reveal the secrets, if you like, of how cancers start and how to stop them starting.

Jennifer Dixon:

So we must leave it there. Big thanks to my guests today, Dr Kimmie Ng, and Dr Charlie Swanton. And meantime, thanks to my colleagues Leo Ewbank and Sean Agass at the Health Foundation, to Paddy and his team at Malt Productions. And it's goodbye from me, Jennifer Dixon.