Tackling colon cancer, with Dr. Andy Chan

Over the past few decades, rates of colon cancer have declined in people over 65 — but they’ve doubled in people under 50. 

By 2030, colon cancer (also called bowel or colorectal cancer) is expected to be the leading cause of cancer-related death in this age group.

He discusses the critical role of diet in cancer risk and what steps you can take to reduce it.

Dr. Andy Chan is a professor of medicine at Harvard Medical School and the program director for gastroenterology training at Massachusetts General Hospital.

If you want to uncover the right foods for your body, head to zoe.com/podcast, and get 10% off your personalized nutrition program.

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Episode transcripts are available here.

Transcript

[00:00:00] Jonathan Wolf: Welcome to ZOE Science & Nutrition, where world-leading scientists explain how their research can improve your health.

Today, colon cancer, also known as bowel or colorectal cancer: We're discussing the causes, the links to gut health, and what to do to reduce your risk. 

Let's start with some good news; today, fewer people over the age of 50 are dying of bowel cancer. But unfortunately, this isn't the whole story. Alarmingly, for younger people, cases are rising and by 2030, the American Cancer Society expects that colon cancer will be the leading cause of cancer-related death for under 50s.

Today's guest is a Harvard Medical School professor and program director for gastroenterology training at Massachusetts General Hospital. ZOE are also lucky to have him on our scientific advisory board. In this episode, Dr. Andy Chan tells us why changes in our gut may be putting us at risk and what we can do about it.

Andy, thank you for joining me today. 

[00:01:20] Dr. Andy Chan: Pleasure to be here, Jonathan. 

[00:01:21] Jonathan Wolf: So we have a tradition here at ZOE, which we have intentionally designed to be really hard for professors and academics, where we have a quick-fire round of questions from our listeners, and we have these very strict rules, Andy. You can say yes or no, or if you absolutely have to, you can have up to a one-sentence answer.

Are you willing to give it a go? 

[00:01:45] Dr. Andy Chan: Okay, I'll give it my best. 

[00:01:47] Jonathan Wolf: All right, brilliant. Is colon cancer a risk for people under 50? 

[00:01:53] Dr. Andy Chan: Yes. 

[00:01:54] Jonathan Wolf: Is there a link between colon cancer and your gut microbiome? 

[00:01:59] Dr. Andy Chan: Yes. 

[00:02:00] Jonathan Wolf: Can inflammation increase the risk of cancer? 

[00:02:03] Dr. Andy Chan: Yes. 

[00:02:04] Jonathan Wolf: Could the way you cook your meat affect whether you get colon cancer?

[00:02:10] Dr. Andy Chan: Yes. 

[00:02:11] Jonathan Wolf: Can changing your diet lower your risk of getting most cancers? 

[00:02:15] Dr. Andy Chan: Yes

[00:02:16] Jonathan Wolf: I think already people are going to be really interested in those answers. Now you can have a whole sentence or two. What's the most common misconception that you hear about colon cancer? 

[00:02:27] Dr. Andy Chan: I think the most common misconception nowadays is that colon cancer is a disease of older people.

I think we traditionally have thought about cancer as being a disease of older adults. But what I think many people don't know is that over the last several decades, maybe since the 1990s, at least in the U.S., and maybe a little bit afterwards in the U.K., we've started to see really sharp increases in the incidence of colorectal cancer in people under the age of 50.

So now I think people have to appreciate that this is a disease that affects younger adults as well as older adults and people need to be thinking about it at increasingly younger ages.

[00:03:10] Jonathan Wolf: Today we're talking about colon cancer, and there's definitely different terminologies around the world.

So I know colorectal cancer is a very common way it's described in the States. Bowel cancer very commonly how it's described in the U.K. And so for consistency, we agreed we were going to call it colon cancer today and hopefully make that work across the globe. 

Now, just as you've just been saying, the first thing that I wanted to mention is that when our team began researching this episode, one of the things they immediately uncovered was in the last few years, these instances of colon cancer have been increasing at an alarming rate in people under 50.

And the second thing I want to mention is that when we asked our audience for questions about the topic, by far the most common question was, when should I start getting screened, and how often? 

So I know we'll be discussing these later in the episode. But before we do, Andy, can I just start at the very beginning?

What is colon cancer? 

[00:04:04] Dr. Andy Chan: Right. So as you mentioned, you know, there are different terms for what we're calling colon cancer today. And that essentially is where people develop a cancer or a tumor in their large intestine or large bowel. 

And so this is the segment of your intestine in which your food eventually ends up, and your digestive products ends up, and is used to really form bowel movements so that you can efficiently and effectively absorb nutrients, absorb water from the food that you eat, and then expel waste products.

And the colon is the large bowel where, you know, you have this reservoir, if you will, for your bowel movements to sit before it's expressed into the toilet ultimately. And within this segment of your intestine, there is the potential that you can have normal cells develop into small tumors known as colon polyps, and those colon polyps can over time become colon cancers.

And those cancers ultimately can grow larger and invade into potentially the bloodstream and also spread to other parts of the body. 

[00:05:14] Jonathan Wolf: And Andy, this is the first time that we've actually discussed cancer on the podcast and I'm sure not the last one. So I sort of want to ask you an even simpler question, I guess, within that story you're describing, which started with these small tumors you described that then become a cancer.

What is that? What's the difference between a cell like what was there before and this tumor thing, what does it mean for something to be a cancer? 

[00:05:38] Dr. Andy Chan: So your normal cells turn over. So for example, in the colon, you have normal cells that line the colon. And those are the cells that really do its job in terms of absorbing water, the kinds of things that it needs to do to actually form bowel movements.

But sometimes those cells can grow in an uncontrolled way. So those small cells that normally turn over and kind of live out a lifespan and then die off sometimes can kind of grow uncontrollably and actually live much longer than they're supposed to live and sometimes live in sort of an indefinite way. And if that's the case, they can grow into what we call polyps.

In other words, they can grow into little growths in the colon lining that can get gradually larger and eventually start to get large enough that they actually start to maybe even invade into the lower layers of the colon and that's where we start to call it a cancer. 

It's essentially a process in which cells grow in an uncontrolled way and that ultimately leads to a detrimental effect on surrounding structures in the body. And also if it eventually leads to growth into the bloodstream and those cells start to break off and start to form in other parts of the body, it can grow in other parts of the body and cause what we call metastases or tumors that are in other parts of the body and where they're not supposed to be, and that can be an area where you get symptoms as well.

[00:07:13] Jonathan Wolf: And so for for someone who does experience this, are you normally aware quite early on in this experience that you have this disease? Do you only discover about it at the point when you describe this, you know, really scary idea that it's, I think you said metastasized, gone somewhere else?

[00:07:29] Dr. Andy Chan: It's a good question. It's variable. I would say people can develop symptoms of cancer. At any stage, although it's quite clear that the symptoms of cancer become much more common and much more pronounced as the cancers get larger and more advanced. 

And so certainly when cancers start to get bigger and really start to impinge on other structures in the body or when they start to spread, that's when people really more often than not develop symptoms.

It's possible to get symptoms at an earlier stage and some of those symptoms are more subtle. But some people can really have no symptoms and have early-stage cancer. 

And I know later, we'll talk a little bit more about screening, but that's really where there is that kind of challenge, is that early stages of cancer, where cancers are more circumscribed or smaller or easier to treat, oftentimes are less likely to cause symptoms. 

So being very vigilant about some very early symptoms is important but also that becomes the basis for why in the end we end up trying to screen. 

[00:08:46] Jonathan Wolf: All right. So you scared everybody listening to this at this point. 

I think the natural follow-up question is who normally is affected by this? Like how common is colon cancer? And do we understand why someone might get it or not? 

[00:09:02] Dr. Andy Chan: So colon cancer is a cancer which is one of the more common types of cancer. So among both men and women combined colon cancer, is one of the second or third leading causes of cancer death, depending on where you are in the world.

Certainly for women, lung and breast cancer are ahead of colon cancer, and for men lung and prostate cancer are more common than colon cancer. But when you combine men and women, colon cancer becomes the second leading cause of cancer death. And so it's a problem generally across different parts of the world.

And we do also recognize that colon cancer is often a cancer that is caught at a later stage when the symptoms can be very severe, when there is significant complications related to the cancers themselves. And ultimately if they're spread throughout the body, they're at a point where it's oftentimes not curable.

[00:10:04] Jonathan Wolf: Got it. So what you're saying is because of the type of cancer often it's quite developed by the time you see it. And therefore sort of there's a higher risk that it might have already spread. Andy, is that what you're saying? And that it's going to be harder to deal with. Am I understanding that?

[00:10:20] Dr. Andy Chan: Exactly. And I think also, because of the fact that the colon is obviously such a vital part of your health, obviously what we eat, our digestion are so important for our overall health. When there is a cancer in the colon, it can be really devastating in terms of symptoms because of the kinds of things that can develop from that cancer in terms of the difficulty in staying nourished, being able to pass your bowel movements, also the pain that can result from cancers in the colon.

So it can be a very difficult and challenging disease when diagnosed late. 

[00:10:58] Jonathan Wolf: Which sounds terrible. 

Could you answer maybe that question that you sort of touched on right at the beginning about the demographics of who is getting it because you described this idea that historically we thought of cancer as being something you got later in life. But I think, you know, that is really less true for this cancer today. 

[00:11:22] Dr. Andy Chan: Yes. So that’s what I think the new reality is for colon cancer. I think that colon cancer, again, in the past has been traditionally thought of as something you develop when you're older, particularly as you get into your late 50s and 60s, that was kind of when people really started to be at risk for the disease.

Having colon cancer, you know, when you were less than 50 was very, very rare. And as doctors, I know we rarely saw a patient who developed colon cancer at a young age. Now we're seeing those patients come into our clinic all the time.

So just to give you a sense at this point in time in the U.S. at least, 20% of people who develop colon cancer are actually under the age of 50. And that's a real striking statistic. 

People who were, for example, born in the 1990s are at twofold higher risk of developing colon cancer now compared to people who were born in the 1950s. 

So there's been a real trend in the population where people who have been born in more recent decades have been at markedly increased risk compared to people born in previous decades at the same age.

[00:12:42] Jonathan Wolf: That's pretty extraordinary, Andy. You're saying the rate of this cancer has doubled in young people, even despite all of our advances, you think in medical care and you know, how we hopefully look after ourselves. 

[00:12:57] Dr. Andy Chan: Yes. So, I mean, I think one sort of stark reality is that we've actually had a lot of success in actually, you know, reducing the rates of coronal cancer overall. 

But all those successes have come in people that are, you know, older. Particularly people over the age of 65. At least in the U. S., the rates of colon cancer have declined markedly in people over the age of 65 on an annual basis, since the 1990s. 

That may be due to improvements in screening, it may be due to improvements in lifestyle, etc. But in contrast, the rates have really increased in people younger than 55, such that we see that people who are in those younger age groups have twofold higher risk of developing colon cancer compared to people who were at that age, you know, in the 1950s, 1960s.

So it's a real demographic shift in the disease. 

[00:13:52] Jonathan Wolf: And I think you said something to me before we started the show that this may end up being the most common cancer for certain younger people. Can you shed some light on that? 

[00:14:03] Dr. Andy Chan: In the U.S., the American Cancer Society just came out with a very sobering report that statistics are such that now the leading cause of cancer death in people younger than 50 among men is colon cancer.

[00:14:17] Jonathan Wolf: The leading cause of cancer death for men under 50 is now colon cancer. 

[00:14:23] Dr. Andy Chan: And by 2030, they estimate that it will become the leading cause of cancer death for both men and women. So that's a real change from where we were, you know, 10, 20 years ago. 

[00:14:34] Jonathan Wolf: And I feel like that is a long way from the common conception because you're actually saying that as a cause of death, for example, that would actually be higher than breast cancer for women under 50 in just a few years. Is that correct? 

[00:14:50] Dr. Andy Chan: Exactly. Yeah. 

[00:14:51] Jonathan Wolf: Which I feel is, and it obviously in no way reduces the seriousness of breast cancer or any other cancer, but it does suggest that there is not a popular understanding of just how common this is becoming as a cancer for younger people. 

[00:15:06] Dr. Andy Chan: Correct. Yeah. I mean, I think that's another trend that we're seeing. We're also seeing that, for example, breast cancer incidence is rising also in younger women. Not at quite the rate of increase as we're seeing with colon cancer.

So cancers in general seem to be shifting downward in terms of when the age at which they're starting to first present. But the increases are the most striking for cancers of the gastrointestinal tract.

[00:15:33] Jonathan Wolf: So Andy, I have to ask. What's going on? 

[00:15:35] Dr. Andy Chan: Well, that's the big question in the field. I think there's been a lot of obvious interest in trying to understand why this trend is occurring. Because, you know, only by understanding why it's occurring can we actually start to figure out how to reverse the trend.

So there have been a number of hypotheses and a number of risk factors that have been characterized based on the studies that we have underway now. This is a research area that my group is particularly interested in, and I think what we've wanted to focus in on are things that we know are risk factors for colon cancer more broadly, to see if they might be playing a particular role in younger adults.

First and foremost in that has been I think the trends that we've seen population-wide, at least in the U.S., and also most other countries, in the rising incidence of overweight and obesity.  Those are risk factors for colon cancer in older adults. So it's not surprising that they also turn out to be important risk factors for colon cancer and younger people.

And we all know that obesity and overweight have been rising as well in the population over the last several decades. So some of that increase in cancer rates might also be attributable to some of those increases we're seeing in overweight and obesity. So that's one factor that we know is important.

The second area that we are really interested in knowing more about is the role of diet. I think that our diet has changed appreciably over the last several decades in many ways, as you probably can glean from sort of how we think about diet and risk with respect to overweight and obesity.

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Some of those same dietary factors may be driving colon cancer rates as well. We know people, for example eat more concentrated sweets, they eat more meat and those are risk factors that we know also are risk factors for colon cancer. So some of those population trends and those dietary factors may be also driving risk, in younger people.

There might be also some unique components of food that we're still really delving more deeply into. We know that our diets now as compared to 10, 20 years ago are much higher in what we call ultra-processed foods. So foods that are designed to be highly palatable, easy to eat, you know, have a lot of convenience built into them.

Our foods that have really increased in consumption over the last several decades and ultra-processed foods have been linked to cancer rates as well. 

The other area that's also of interest for people is the changes in the way they consume alcohol. Alcohol, particularly heavy alcohol use is a risk factor for colon cancer, and we know drinking habits have changed a lot again over the last several decades, even preceding the pandemic. So that has been something that we've been studying in a more intensive way. 

And then some of the things that are particularly interesting also is to think about some of the overlooked dimensions of these risk factors. I think we think about these as being risk factors but also need to think about when during the life course are these risk factors most important. 

Is it the fact that people are, you know, really, maybe, eating more of these unhealthy foods at an earlier point in their life cycle, like when they're adolescents or young adults, than in past years, that may be driving risk in a different way.

We also know there are dimensions about when we eat food and when we drink which, is important. So, for example, we, tend to drink more now in large quantities, it's so-called binge drinking. So is binge drinking a particular risk factor for cancer in a way that more consistent low-level drinking was not?

These are all kind of really important dimensions of exposures and risk factors that we're considering. 

And then last, I think we all recognize that there are many people that are younger than 50 that develop colon cancer that don't have any of these risk factors. I have many patients that come to me that are lean, they've never been overweight, they eat a very healthy diet, they don't consume large amounts of meat, they really watch what they eat, yet still get the disease.

So, you know, this is not a complete explanation for why we're seeing the trends. There's other things out there that are driving risk that really are, at this point, speculative. I think we need to investigate further. Are there environmental factors, pollutants, things like that have still been not characterized that we need to mainly investigate further?

We recognize that cancer is a disease ultimately of metabolic health, especially colon cancer. We think colon cancer in particular is a cancer that's driven by raw state of metabolic health. And among cancers, we think colon cancer is probably the cancer that is the most likely to be related to diet and what we eat, which is not surprising because obviously the color is exposed to what we eat.

[00:21:12] Jonathan Wolf: Could you just explain for a minute what a disease of metabolic health means for our listeners? 

[00:21:18] Dr. Andy Chan: Sure. So, just to back up, I mean, I think our interest in this came around because we recognize that as you sort of tick through the different cancers and sort of what are the cancers for which diet is the most likely to be linked. Colon cancer is probably the leading cancer that's diet-related. 

We also know that colon cancer is particularly related to other factors that we associate with how we metabolize food and our metabolism more broadly. 

What I mean by that is there's been a lot of interest in, for example, the fact that again, people with overweight obesity are more likely to develop colon cancer. People with diabetes have a higher risk of colon cancer. People who have so-called metabolic syndrome or a constellation of sort of conditions related to what we call insulin resistance are more likely to develop colon cancer.

And insulin itself has been thought to be a risk factor for colon cancer. The high levels of insulin in the blood, for example, drive the uncontrolled growth of cells in the colon. And so is, for example, the sort of high levels of insulin that occur in related to metabolic diseases, a driver of colon cancer. I think that's been really, a leading hypothesis too.

So I think of the cancers of the body, colon cancer is the one that seems to be most linked to metabolism or how we eat our food, how our body processes food and our body's response to food. 

[00:22:55] Jonathan Wolf: I think you're saying that you might increase your risk of colon cancer, not just directly because the food you eat is sort of directly like this carcinogen, like we're all used to being taught by, you know, our governments over the last 50 years.

But actually, if you're eating this you know, ultra-processed food or whatever it is, year after year, then you get all of this bad control over your blood sugars and your blood fats and all these sorts of things. And that itself then becomes this risk factor for the colon cancer. Did I understand that?

[00:23:27] Dr. Andy Chan: Yeah, no, that's a very good way to summarize it, that there might be some specific effect that the food we eat is having on cancer. But also we know that the food we eat affects exactly what you've mentioned, it affects our overall level of inflammation in the body. It affects our overall metabolic ability to metabolize and process food and sort of our metabolic biochemical functions may be changed.

We may have less ability to control our blood sugar, to control our blood lipids. So the fact that diet can, for example, raise our blood sugar, raise our insulin levels, raise our inflammatory markers, also raise some of the other lipid markers that we know may cause again inflammation or diseases in our blood vessels, may also be causing problems with our ability to prevent our colon from growing tumors and developing cancer.

[00:24:32] Jonathan Wolf: And Andy, I'm sitting there looking at the beautiful view in your office behind you, as you say that, and it reminds me of the first time that I met you, which must be seven years ago, I think now, when I was with my co-founder, Professor Tim Spector. And talk about this idea of kicking off this very first PREDICT 1 study, looking at the impact of diet, but particularly about sort of the microbiome and how that tied into diet and different personalized results. And rather amazed to discover how interested you were, which is when you started working with us now a long time ago. 

So I would love to discuss because I know this is a big part of your personal research and interest, how the gut microbiome sort of links into the things that you're describing. To what extent you believe that the health of your microbiome is linked to your risk of developing colon cancer?

And I guess what the status is, of your research and others around that today, because I know that this has been a big part of why you've been really interested to and helped us a lot in the research we've been doing. 

[00:25:42] Dr. Andy Chan: Yeah. So, as you mentioned, it's been a terrific history we've shared together and working together on the ZOE PREDICT studies here at Mass. General.

And our interest, I think, was driven largely because we are so interested in diet and the gut microbiome and what its impact is on health in general. So just as we really recognize that diet was a major sort of risk factor or elements of colon cancer risk, in parallel, we also recognize that there was increasing data that the gut microbiome was an important factor in the development of colorectal cancer.

There have been and there have continued to be a large number of experimental and animal studies that show that the gut microbiome is linked to colon cancer in a very direct way. So you can induce cancers by changing for example, a mouse or an animal's microbiome, and you can reverse cancer by changing an animal's in a positive way.

So that, that data is really, really compelling. That shows that linkage between gut microbiome and cancer and these experimental models. 

[00:27:04] Jonathan Wolf: Andy, just before you move on, I just want to make sure that I got that right, because there's often a debate about the microbiome and to what extent it has any real cause rather than just being an indicator.

But here you're saying that in animals, they've literally been able to, you put the sort of the wrong bugs in and you can get this cancer. And equally well, if you change them for the better bugs, you can actually prevent the cancer.

[00:27:30] Dr. Andy Chan: Exactly right. Yeah. So I mean there's cause and effect that we can show in experimental models and animals that I think has been very compelling.

At the same time, we are seeing increasing data in humans that the gut microbiome is an important risk factor. There have been a large number of epidemiological studies that have shown, for example, that people who develop colon cancer have a different gut microbiome compared to people that do not.

And those changes in the gut microbiome are changes that are similar to the changes that you see in mice that develop cancer more directly.

So, you know, there's a very strong kind of convergence of that human data with the mouse data that suggests that what we're seeing in experiments are likely to be very relevant to the human condition.

I think there's also a large number of studies that have shown that people who have what we call a disrupted gut microbiome or have disruption of gut microbiome have a higher risk of colon cancer. 

So in particular, there are several studies that have shown that people who are exposed to large amounts of antibiotics, particularly when they're younger, which we know is almost like a nuclear weapon against your gut microbiome, that those people have higher rates of cancer and colon cancer down the road as well.

And I think now there is also more information about the presence of gut microbes actually in the colon tumors themselves. So, when you actually look at the colon cancers that develop in people and actually do very targeted experiments where you can try to identify if there are particular gut microbes in those tumors, they're identifying some of these bacteria that we know cause cancer in animals.

So I think there's really compelling data that what we're seeing as cause and effect to end in animals is likely to be causal in humans as well. 

[00:29:48] Jonathan Wolf: Andy, that's a whole bunch of amazing research. I could dive into any of that for the next half an hour. But I guess my first question is generally when we've done a lot of podcasts talking about the microbiome and obviously a lot of science is about it as well, often the discussion is more about this as a community. 

So I often think about it a bit like a coral reef, right? With hundreds of different species sort of interacting and it's that total interaction which has this effect on our health. 

But that's obviously for a healthier situation and here we're now talking about cancer and I heard you mention the idea of specific bacteria being found inside the tumors. 

Are you suggesting that there might be specific microbes that are sort of directly the cause of these cancers? Or is this more like this pattern of maybe, you know, you've got too many of the bad ones and not enough of the good ones? 

I guess, both what does the science say, but also I know you're, we're at the very cutting edge, what's your own guess on this at the moment?

[00:30:46] Dr. Andy Chan: I think that the science is evolving. So I think there are very clear data that your community of gut microbes can be a predisposing factor for the development of colon cancer.

So you can imagine that your gut microbiome is kind of an expression of your diet. So what you eat actually influences what gut, gut microbes you have.

Also, what you eat is ultimately the stuff that those gut microbes break down and those gut microbes and what they break down ultimately release metabolic products that ultimately in influence gut health. And we believe better gut health reduces risk of cancer. 

So there is an overall effect of sort of one's gut microbiome that seems to be a risk factor for cancer and it's not just specific microbes that are what we need to be concerned about. 

But, at the same time, there's a parallel line of research in which there are some gut microbes that seem to be particularly relevant to the development of cancer. The question is whether those specific gut microbes are important in sort of the initial development of the cancer, or are they something that kind of help or maybe factors in sort of how cancers develop and progress over time?

The bottom line is I think it's both. I think it's kind of one's overall microbiome and also ultimately there might be some specific microbes that play a role in different stages of when a cancer develops. 

[00:32:23] Jonathan Wolf: It sounds like you're saying it probably isn't like a traditional infection where there's just this one special bacteria that gets into your gut and therefore means that you're going to get this cancer.

It's more like somehow your microbiome ecosystem is degraded like your microbiome health is worse. You've probably got all these other factors from the food that you eat that's affecting you. And then these bad guys come along and it sort of got the right environment for them to suddenly prosper. 

Is that is that my simple analogy for what you're saying?

[00:32:56] Dr. Andy Chan: Yeah, it may lead to a situation where specific microbes then have a sort of selective advantage to kind of grow and further propagate or perpetuate a tumor. 

So I think that that's a likely sort of way to think about it. A likely scenario in which, you know, the gut microbiome is related, but I think it's an open question.

I think there's a lot of research and there's a possibility that there may be specific microbes that are particularly detrimental. But I don't think that explains all of what we're seeing in colon cancer. 

I think for the most part, we're probably dealing with an overall disrupted gut microbiome that then potentially tends to let certain bacteria overtake one's physiology and can be the ones that are particularly harmful down the road.

[00:33:45] Jonathan Wolf: I just want to go back to this thing that you mentioned really fast in passing, Andy. Which is that increasing the amount of antibiotics that you have as a child could really increase your risk of cancer. 

[00:33:58] Dr. Andy Chan: Yeah, so I think the studies that we've done as well as other groups have shown that people who are exposed to more antibiotics in early adulthood or even in childhood seem to have a higher risk of developing colon polyps or colon cancer in the future. 

But that isn't meant to alarm people. I don't think we're saying that, for example, people shouldn't be using antibiotics if they need to be on them. Certainly there are very important reasons for why people need to be on antibiotics. 

What I think those studies do indicate to us is that people who are more likely to have some disruption in their gut microbiome which we believe is a consequence of being on antibiotics for a long period of time, that disruption in the gut microbiome may have some lingering effects down the road.

So I think it gives us some more evidence to suggest that the gut microbiome is important in colon cancer risk. 

Of course this data is correlation. It doesn't prove cause and effect, but I think it does give us a strong suggestion of how important the gut microbiome ultimately is for our cancer risk.

[00:35:04] Jonathan Wolf: And Andy, there are very varying levels of antibiotic prescription across different developed countries. And the U.S. is one of the countries that has very high levels of prescription of antibiotics versus some rich European countries that have very good health outcomes, just to, you know, sort of compare like for like.

Does this cause you to question whether, obviously it's life-saving in a whole bunch of cases, but there could also be a case that is sort of over-prescribed. Because historically, we felt that there was no downside to the antibiotics. And does this sort of suggest that we need to be sort of more thoughtful than perhaps we have been in the past?

[00:35:48] Dr. Andy Chan: I think that's true. I mean, we definitely overuse antibiotics. I think we have recognized that’s a longstanding problem in the U.S. in particular.

So it does suggest that we need to be more conscious and judicious in how we use antibiotics and really have a good reason to use them or we do use them. Just because that's good stewardship in terms of being able to make sure that the right people get them, not only for this sort of question about the effects on the gut microbiome but also just in terms of preventing issues with antibiotics resistance, et cetera. 

So there's many reasons for why we have to be more careful with the use of antibiotics and use them when they're only very appropriate. 

[00:36:34] Jonathan Wolf: I think that's really interesting. I've definitely changed my own view as I think about my children. So my son is 16,  I didn't think about this at all. My daughter is four, that was after ZOE and my wife's a doctor as you know, so she's really in charge of all medical decisions. 

But I'm definitely really shifting my view that you should have antibiotics if you're really sick. But I think I would have historically been like, Oh, she's a bit sick. we should really try and get the doctor to give antibiotics. Because you get this sort of instant win. 

And I think about it a bit now, like the instant high you might have of having a piece of cake and a candy. We know that's not good for you in the long run, doesn't mean you should never do it.

And so I have definitely shifted my view because of that and also like my own experience with having very serious antibiotics a year ago after a minor surgery and just seeing the incredible decimation of my own microbiome and the time it's taken to go back. That's definitely made me think, not that you should never do it, but that you wouldn't want to do it if you didn't need it.

[00:37:35] Dr. Andy Chan: They're powerful drugs. I mean, obviously, you know, they're designed to do certain things that are important to our health. And when again, there's a clear infection and there's a clear disease to be treated, there's no better drug. 

But if the reason to use it is not very clear, or you're just sort of using it just to kind of make yourself feel better, then it's more likely than not that it's not going to probably make a difference in sort of the symptoms you're having and could kind of cause these longer-term consequences. 

So I think doctors and patients alike, I think are becoming more aware that they need to think carefully before they start antibiotics. 

[00:38:15] Jonathan Wolf: I'd love to shift and talk about what are the actionable things that our audience could do to lower their risk of getting colon cancer.

And as I mentioned right at the start of the episode, by far the most frequently asked question, interestingly, was about screening. So, could you maybe start with that? Who should be getting screenings? How often? And I know that what actually happens is different country by country, but just looking at this to start with as a researcher and expert, what would be your advice?

[00:38:45] Dr. Andy Chan: So as you did mention, things vary from country to country. So I'll speak to this from the standpoint of being a physician in the U.S. 

So screening is something that we know saves lives. It's recommended by multiple expert bodies here in the U.S. as well as internationally, that colon cancer screening is important because as I mentioned, earlier at the top of the podcast that most colon cancers in early stages are not symptomatic.

So you can't wait for people to get symptoms to diagnose cancer in an early stage. And we also know that diagnosing on an early stage is the critical factor in terms of whether someone can be cured of their disease. 

So someone who, for example, is diagnosed with stage 1 or early stage colon cancer, or even if they have very large polyps, those people can be cured of cancer over 90-95% of the time through surgery and surgery alone.

[00:39:47] Jonathan Wolf: So 90-95% of the time you can actually cure this cancer. So I just want to make sure I... It's the most positive thing you've said all episode, Andy. 

[00:39:57] Dr. Andy Chan: So that's why we put such a strong emphasis on screening is because we can use screening as a way to detect cancer early, before symptoms develop and when it's treatable.

And ultimately, screening has been shown to reduce death from colon cancer in the long term. 

Ten years ago, we only recommended screening for people over the age of 50. But in recognition of this trend toward younger people getting colon cancer over the last couple of years, the screening age has now shifted such that we recommend screening for anybody over the age of 45. That's for people in the general population. 

Now if you have a family history of colon cancer, then we recommend you start screening earlier. Either at the age of 40 or 10 years before your relative got colon cancer. And that's been something that I think has been the reason why we're seeing the declining incidents of colon cancer in older people.

It's because of these screening programs that have been really pushed across the board in the U.S. 

[00:41:06] Jonathan Wolf: And how does it work, Andy? What do you need to do to be screened for this disease? 

[00:41:11] Dr. Andy Chan: So screening for colon cancer can take a number of approaches. I sort of divide it up into two categories of screening.

One category of screening is what we call invasive screening or what we do in the U.S., which is a colonoscopy. So by invasive, it means coming in for a medical test in which you have to drink a laxative to clear out your bowel. You come in the next day and you get some sedatives and you undergo what's called a colonoscopy, which is where a physician like myself passes a small, flexible camera through your rectum into your colon to look for polyps and cancer.

It's something that allows us to both look for cancers and look for polyps, but also remove them if we see them during the exam and take them out to try to prevent them from developing into cancers. 

The other form of screening is what we call non-invasive screening. These are tests which don't require you to come in to see a doctor, don't require you to get sedatives or undergo any procedure. And these are tests in which we basically take a small sample of your bowel movement and either look for blood or look for some DNA mutations in your bowel movements.

Those screening tests are done in the comfort of your home and you send them in to the doctor to read. And if you see anything abnormal on those tests, then you may be referred for that colonoscopy I mentioned with a doctor and both are reasonable options for screening. 

[00:42:48] Jonathan Wolf: Got it. So there is actually the second one where basically you're just getting a sort of sample of your poop and testing it actually is quite effective in terms of picking up these earlier stage cancers?

[00:42:59] Dr. Andy Chan: Yes. So the screening that you can do with just a bowel movement will pick up cancers at a very high rate. It's not as good at picking up polyps. Again, polyps, as I mentioned is that sort of early tumor. It's not yet a cancer, but it can become a cancer. Those polyps are kind of even earlier in the process of colon tissue becoming cancer.

And so if you see a polyp and find a polyp, you take it out because you want to kind of interrupt that progression to a cancer. The stool tests are not very good at picking up polyps. The colonoscopies are definitely better at picking up polyps, which is why some people feel more comfortable having the more invasive test, the colonoscopy, whereas other people are more comfortable having the noninvasive stool-based test. 

And again, depending on the country, you may be restricted in terms of what you have access to. So, for example, in the U.K., stool-based testing is what's recommended. Colonoscopies are reserved really for people who have positive stool-based screening tests. In other words, a screening test that's abnormal or have other symptoms or risk factors that require them to have the colonoscopy. 

So I would say that a lot of people, particularly young people, should not be afraid to get screened. I think if you're thinking screenings that are very involved, kind of invasive tests, it doesn't have to be. The stool-based tests are really quite good. 

And really what we feel in the field is that the best screening test and the best way to prevent cancer is the one that you can do and the one that gets done. And so if you can, you submit a little sample of poop, and that's all you need to do. I think that that goes a long way toward prevention.

[00:44:44] Jonathan Wolf: Can I talk about how you could change your diet in order to reduce your risk of colon cancer? 

[00:44:50] Dr. Andy Chan: Yes, so that again, I think is something that also we need to pay more attention to. I think there is a justified focus on screening. I think it is such an effective tool and so we should do as much as we can to get our population screened. 

But as you mentioned screening is not without cost and also we can't screen our entire population, certainly in the U.S. even. We lowered the screening age to start at 45, but people are still at risk for cancer younger than 45, but we don't have the resources to screen everybody. 

So it's really important to also think about other approaches to prevent colon cancer in addition to screening, and that can be used as a complement to screening. And that certainly involves trying to modify those things that we know are risk factors for colon cancer.

We know that diet is a risk factor, and we know that diet is something that we can modify with some effort. And with some help and the added benefit of sort of working through that pathway is that those modifications we can make in our diet or lifestyle could have some benefits for things other than colon cancer.

So it can obviously reduce our risk of diabetes, heart disease, maybe other cancers. So there’s a lot of cogent reasons to think about lifestyle modification as being really a central component of cancer prevention strategy. 

[00:46:27] Jonathan Wolf: And Andy, are there specific foods or dietary patterns that are really associated with higher risk of colon cancer?

[00:46:34] Dr. Andy Chan: So we'll start with what we know and then we'll start with where we hope to go. 

So what we know is that red meat intake and processed meat is a risk factor for colon cancer. So the International Agency for Cancer Research did a very comprehensive review of dietary risk factors for colon cancer, and they felt the most compelling evidence was for red and processed meat being a risk factor.

So reducing your intake of red and processed meat as much as possible is one key way that you can reduce your cancer risk. 

The other factor I think also that's becoming increasingly important is alcohol. I think trying to reduce alcohol intake is probably important to do. It's not clear whether there's a threshold effect. I think that it's becoming maybe more clear that it's probably a linear risk factor. So the less you drink, the better in terms of your risk for developing a colon cancer.

[00:47:32] Jonathan Wolf: I wanted to ask you about that because I know that on an overall basis, it isn't just like the more you drink, the worse, I've understood from a lot of scientists here. And talking about the advice was ZOE, that sort of like one glass of red wine probably isn't making things any worse at all, but then it gets much worse as you increase. 

But in this case, you're saying it's not like that, even just any amount of alcohol is increasing the risk and it just sort of goes up and up as you drink more.

[00:48:01] Dr. Andy Chan: Yeah, I think it's not clear how steep that curve is. So, you know, it could very well be that there's a little bit of an increase in risk with that one glass of red wine, but as you start to get up to two, three drinks, you start to really get a steep increase in risk.

That sort of dose-response, if you will, I think is still something that we're grappling with. 

[00:48:24] Jonathan Wolf: Okay, so not clear, but so it might be that it's not completely the same, but it's certainly not, it's not the all clear that some people might want it to be who would like to be able to have a glass of wine.

[00:48:35] Dr. Andy Chan: Right, right. So those are the established risk factors. 

And I think going to where we want to be, I think there is increasing data now that diets that are higher in sort of whole grains and fibers may be protective against colon cancer and that may be mediated by potentially its effect on the gut microbiome.

So one of the questions that we hope to answer in our Grand Challenge Award to investigate not only causes of early-onset cancer but also agents to reversal early onset cancer is, are there specific diets that we can start to understand could be tailored in a way to promote a gut microbiome that is associated with, with lower cancer risk?

So by combining kind of the information we're developing and learning about, what sort of gut microbiome is associated with colon cancer, it stands to reason that we can start to maybe develop a diet that may actually modify the microbiome in a way that's healthier and that's associated with low risk of cancer.

And that may in part be related to fiber, but also may be related to other dietary components as well. 

[00:49:51] Jonathan Wolf: And Andy, we had a lot of questions sort of about two particular aspects of food, so I just want to make sure I ask them really clearly. 

One question was, should we be concerned about nitrites found commonly in deli meals? I think you just mentioned something about processed meats, I'd love to understand that. 

And another one was back to the question I asked at the beginning about the temperature at which you cook meats, and is it important whether you're eating sort of raw red meat or cooked. 

Do you have any views on either of these?

[00:50:20] Dr. Andy Chan: Yeah, so the association between red meat and also processed meat and colon cancer, I think is quite compelling based on the epidemiological studies. 

The mechanism by which those factors can lead to cancer are less clear. From experimental data, there is a suspicion that maybe nitrates could be a factor.

But there's also strong data that supports that it's not necessarily the meats themselves, but how they're prepared. So nitrates being a preservative is one factor. 

[00:50:59] Jonathan Wolf: And this is all stuff like sort of sausages and salamis and bacons and these sorts of things, Andy? Is that what we're talking about when we talk about processed meats?

[00:51:08] Dr. Andy Chan: Correct. Luncheon meats, you know, bacon for sure, are particularly linked to cancer risk.

The other dimension is how we cook the meat, as you mentioned. So, I think one of the strong hypotheses linking meat to cancer risk has been through the production of certain carcinogens that are generated when you cook meat at high temperatures, in particular the generation of what we call heterocyclic amines. And that occurs when you char meat. 

So when you grill it, or when you cook at a really high temperature, you tend to form these heterocyclic amines. And those amines, when ingested, causes cancer in animals. So that is a potential mechanism also. So there's I think, a lot of work to be done to further characterize other potential mechanisms.

There’s also, I think, quite compelling data that meat alters the gut microbiome in a way that is detrimental to health. And may lead to some what we call dysbiosis or microbes that are less healthy for you. 

In particular, some of the amino acids in meat and the proteins in meat can help to facilitate the growth of certain bacteria that generate sulfur and sulfur-reducing, sulfur reduction in the colon. And sulfur reduction in the colon can be carcinogenic as well to normal colon cells.

[00:52:35] Jonathan Wolf: And Andy, one of the things that we always say at ZOE with anyone who becomes a member is, you know, nothing's forbidden, nothing's off the table completely. It's sort of about frequency. 

So when you say this, does that mean if you have like one piece of red meat a week, then suddenly, okay, you're straight to seeing Andy with your colon cancer? Or is this about how many times you're eating these foods? 

[00:53:00] Dr. Andy Chan: So for meat in particular, it looks like it's definitely people who consume it more frequently are a particularly high risk. So I don't tell my patients you have to become vegans or vegetarians, but you know, I think obviously there are other healthy alternatives to red meat.

So when possible, I think substituting red meat with fish or seafood, or maybe even chicken could be a good option. But again, I don't tell anyone to be unrealistic about what they can or cannot eat. 

[00:53:30] Jonathan Wolf: We're over time, but I just want to sneak in one final question from our listeners.

Does physical activity play a role? 

[00:53:37] Dr. Andy Chan: Yes. So that is something that probably plays a role. Even independent of overweight obesity, so there have been numerous studies that show people that are more physically active, even independent of their ability to lose weight, are less likely to develop colon cancer.

So staying active is something in addition to diet that can be an important complement to screening. So I think you do have a number of things that you can do to really reduce your risk of cancer and also reduce your risk of other chronic diseases.

[00:54:17] Jonathan Wolf: Amazing. Andy, I have so many more questions. I'm totally over time. I'd like to try and do a quick summary. It's a really new topic for us. So please correct me. And it's also very, very important to get it right. Please correct me if I get anything wrong. 

So we started by explaining what colon cancer is and how you explained that it starts as a tumor in your large intestine which is sort of where your food ends up and also where we know sort of all of these gut bacteria are.

You said that normally you have all these cells in the lining of your gut and they regularly die off, but sometimes they start to grow in this uncontrolled way. That's what starts it to be a tumor. That small tumor sort of gets bigger and bigger and becomes a cancer. 

Eventually that cancer, some of these cells break off and then they go elsewhere in your bloodstream. And then it spreads to the rest of your body.  

And what you said is it's often caught late because often there are no symptoms early on. So it can go quite a long way in that process before it's caught. 

And as a result of this, it's a much bigger deal than many listeners, including myself, had realized. So you said it's the second or third leading cause of death from cancer in the U.S. By 2030, it will be the leading cause of cancer for men and women under the age of 50.

And that the rates of getting this cancer have actually doubled in 40 years. You describe people born in the 1990s and 1950s, so that's a really big difference.

Then we talked a bit about the role of the microbiome, and you said that actually it's really been proven in animals, the sort of causal effect of the gut microbiome on colon cancer. With human beings that's not all the case yet, but you're obviously pretty convinced that it plays a role in there.

And you said, for example, that people with colon cancer have clear changes in their microbiome compared to people who don't. That we can now find specific bacteria actually inside the tumors that are inside these cancers. 

And then you shared this rather terrifying fact that exposure to antibiotics since you were a child, like higher levels of that actually increases your risk of getting this cancer. And I think you mentioned this view that in your opinion, we do overuse antibiotics in the states. 

Then the good news is we talked about what you can do. And what's really exciting, I think, is actually there's an awful lot that we can do. So I think that's after all of that slightly scary side, a really positive side.

So you said firstly, screening is extremely effective. So you said that 90-95% of early stage colon cancers, if they're caught at that point, can be cured. And that there's now screening that starts at 45 in the U.S. I think you said it was sort of 50 in the U.K. will be different in other countries.

And there's two sorts. There's a colonoscopy, which allows you to also potentially treat some of this, but is obviously more invasive. But you can just get a sample of your poop tested. And actually, this is now very effective. So I think that's, that's very exciting. 

And then you talked about, well, what can everybody do who's listening at home? Because clearly you don't want to get this in the first place. And you also mentioned the fact that these dietary changes affect not just your risk of colon cancer, but affect really sort of all sorts of cancers. 

So the first thing you said is that we know that bad diet leads to higher overall risk of all cancers. So what you eat matters. 

And then specifically for colon cancer, you said there are these sort of traditional advice of which the first is sort of avoid or reduce red meat and highly processed meat like bacon or salami. That's a clear risk factor. That charring your meat is probably part of that risk and the alcohol is a real risk factor. So if you are drinking quite a lot, this is, this is something you should really be thinking about. 

And then I think you said the data is not all there yet, but it really sort of suggests quite strongly that eating more fiber, more of a whole grain diet should be protective against this, possibly because of its impact on the microbiome.

And then right at the end you dropped something fascinating that we haven't had enough time to dig into. So this may be a whole other podcast that physical activity can actually help protect you against cancer, which is amazing because we've talked often on the podcast about its benefits, but the idea that it could actually reduce your risk of cancer is amazing.

[00:58:38] Dr. Andy Chan: Yeah, that's a great summary. If I could just add one last point. 

So you did mention that your audience is global. So I do want to mention that this is although we focus a lot on the U.S. and also the U.K., this trend, I think, in early onset colon cancer is rising around the world. 

So even in countries, for example, like India, which had traditionally seen very low colon cancer risk and possibly that was due to a high level of vegetarian diet, other things, we're seeing also rapid increases there too. So it is a global problem. 

So globally, I think we need to think about not just screening but diet and health because we can't screen in many parts of the world. So I do want people to recognize it's a global problem and so we have to think about diet, lifestyle, physical activity from a global perspective to really prevent and reverse this terrible disease.

[00:59:35] Jonathan Wolf: Andy, thank you so much for that. And for the clarification at the end. It's such a pleasure always working with you and your team. And I'm so glad we could make this podcast happen. I hope we can tempt you back for another one. 

[00:59:47] Dr. Andy Chan: I'd love to. Thank you. 

[00:59:49] Jonathan Wolf: I hope you learned something today and enjoyed the episode.

If you listen to the show regularly, you probably already believe that you can transform your health by changing what you eat. But there's only so much you can learn from general advice on a weekly podcast. If you want to feel much better and live many more healthy years, you need something more.

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As always, I'm your host, Jonathan Wolf. This episode of ZOE Science & Nutrition was produced by Julie Panero, Richard Willan, and Sam Durham. The ZOE Science & Nutrition podcast is not medical advice. It's for general informational purposes only.