What's Causing Cancer Rates to Rise in Gen X and Millennials?

Dr. Diane Reidy-Lagunes:

The headlines are everywhere. Two recent studies from the National Cancer Institute and the American Cancer Society show an uptick in cancer among young adults.

News Footage:

There's growing evidence: Younger people are more likely to develop certain cancers than their parents.

You are more likely to develop cancer in your 30s and 40s if you were born in the 1990s and 1980s, than your parents were who were born in the 1950s and 1940s.

Dr. Diane Reidy-Lagunes:

What could be causing this? Let's talk about it.

Hello, I'm Dr. Diane Reidy-Lagunes from Memorial Sloan Kettering Cancer Center and welcome to Cancer Straight Talk. We're bringing together national experts and patients fighting these diseases to have evidence-based conversations. Our mission is to educate and empower you and your family members to make the right decisions and live happier and healthier lives. For more information on the topics discussed here, or to send us your questions, please visit us at mskcc.org/podcast.

Today we are joined by Dr. Karuna Ganesh, friend of the pod, medical oncologist, and physician-scientist here at MSK. Her work is focused on investigating and treating metastatic gastrointestinal cancers. We are also thrilled to be joined by Dr. Caitlin Murphy. She's an epidemiologist and associate professor at UTHealth Houston School of Public Health. Her research focuses on understanding the causes and outcomes of cancer, specifically in young adults. Karuna and Caitlin, thank you both for joining me today.

As we previously discussed on the podcast, we know that obesity and having a sedentary lifestyle can increase cancer risk, but that doesn't fully account for the increase. Today, we want to talk about it. What else is going on here?

As a GI oncologist, I see many cases of colorectal cancer in younger patients, many of whom are super active and maintain a very healthy lifestyle, some of whom are even marathon runners. So what else is contributing to this trend?

Dr. Murphy, you've conducted population-based research to help us answer why younger, seemingly healthy people are being diagnosed with cancer. For our listeners, a population-based study looks at large groups of people to help understand patterns and trends in health and/or behavior. So Caitlin, can you share with us a little bit of your research and what you're doing, which is really exciting?

Dr. Caitlin Murphy:

As an epidemiologist, I've been really motivated by the increasing incidence rates of a number of cancers across generations like millennials or generation X. And usually when this happens, it clues us in as epidemiologists that exposures in early life may be risk factors. When I say early life, I mean periods during the earliest phases of development like fetal development in the womb, infancy, childhood. Those very, very early periods of life. What could be happening during this important developmental time that's related to the risk of developing cancer in adulthood many, many decades later.

I've been fortunate to work with a cohort – a big group of pregnant women who enrolled in a study back in the 1950s and 60s – and they and their offspring have been followed over time to the present day, so now more than 60 years. It's really allowed us to look at those things in early life that may be linked to cancer many decades later.

We have found things like medications prescribed during pregnancy may be related to risk of colorectal cancer in young adult offspring. We've also identified maternal characteristics, like a mom's BMI before she became pregnant, or how much weight she gained during pregnancy, as important risk factors.

Dr. Diane Reidy-Lagunes:

Why is it that you were able to think that, in this population of young folks that are getting cancer now, it may have happened from a risk as early as when they were in utero in their mom's womb? Like what made us think that that may be a clue as to what's going on?

Dr. Caitlin Murphy:

In epidemiology, we talk a lot about this phenomenon of birth cohort effects. And when that happens, one of the clues is that early life may be important. That's because birth cohorts age and move through life together. So when we see these effects, it tells us that it usually corresponds to a population shift and exposure to some kind of risk factors, and those that happen across the entire life course. So we really want to start to understand what happened in the earliest periods that may have set this cohort on a trajectory of higher risk across their lifetime.

Dr. Diane Reidy-Lagunes:

This idea that maybe an exposure while you were in utero, in your mom's womb, could potentially be a risk factor for colorectal cancer is quite terrifying. Can you share with us some of your research on some of the medications that a pregnant woman may have received or taken that could have increased that risk?

Dr. Caitlin Murphy:

Sure. We've looked at several medications that are commonly prescribed during pregnancy. These include anti-nauseants to help with morning sickness, antibiotics to treat common infections during pregnancy, as well as synthetic hormones often used to prevent preterm birth. And with each of those medications, we've identified an elevated risk of colorectal cancer in the adult offspring.

Dr. Diane Reidy-Lagunes:

Karuna, your research is somewhat linked as well; this idea of the microbiome and that the bacteria in our gut and the types of bacteria that we find may actually increase the risk for the development of colorectal cancers. Could you speak to us a little bit about your work and what you're looking into?

Dr. Karuna Ganesh:

Yes, absolutely. So we are interested in understanding how cancers develop and progress. All cancer ultimately is a combination of things that happen within the cells themselves – usually genetic changes, mutations that occur in the cells – and how those cells then interact with what we call the microenvironment: all of the cells and other stuff around those cells in the context of tissues and organs.

When we are thinking about colorectal cancer, the cells that get mutated and form the cancer are the ones that line the gut. Those are the ones that are in direct contact with the contents of the gut – which of course includes food and everything else that we take in through our mouths, including a variety of environmental exposures – and importantly the gut microbiome, which is this population of bacteria, viruses, and fungi that live with us, in us, and on us. In fact, our bodies are actually comprised of more non-human cells than human cells, and many of those cells actually live inside our guts. So when we develop colon cancers, this is happening in close proximity to this microbiome.

This is where the kind of work that we've heard about from Dr. Murphy becomes very pertinent. When patients are exposed to antibiotics, for example, early in life, we know that that gets rid of what we hopefully think are bad bacteria. But then that also clears up space within the gut for other bacteria to grow, and these can have good or bad effects. This is really what we are looking into.

Can we look at patients who are developing colon cancer earlier in life – patients younger than 45 – and ask whether they have different bacteria in their gut, which in turn may reflect different exposures to antibiotics, other drugs, and to other environmental exposures? Can we try to understand mechanistically what might be driving those cancers to happen earlier in life?

Dr. Diane Reidy-Lagunes:

And just of note for our listeners to understand the enormity of this: colorectal cancer is now the leading cause of death in men younger than 50 years of age, and the second cause of death for women younger than 50. So it's on the rise, and this type of work is critically important.

And it may be that the microbiome is part of the reason, but there may be a lot of other things, right? It almost feels like there is this needle in the haystack, especially if we're trying to go all the way back to in utero to understand those risk factors.

Researchers are also investigating other potential environmental factors and lifestyle changes such as increased alcohol, ultra-processed foods, and the use of PFAS, also known as forever chemicals, which are found in many household products. Are either of you studying this, or do you know of studies related to this?

Dr. Caitlin Murphy:

I'm really interested in the question of environmental chemicals, particularly as it relates to colorectal cancer. Typically, we don't think of colorectal cancer as a cancer caused by environmental chemicals. We tend to think of lifestyle-related risk factors like obesity or diet. But to me, this storyline is just so clear. The manufacturing history of a number of environmental chemicals aligns almost perfectly with the trends that we're seeing in the rise in cancers, both across time and across birth cohort.

But the challenge is, there are millions of chemicals. We can't just pick one to study. I think we have to approach this from a discovery perspective. What, in the millions of possible exposures out there, could be related to this rise in cancer that we're seeing? I think patients would tell you, we don't have time to wait for scientists to test one chemical at a time.

We need new novel approaches to really understand what in the world is going on here. And those tools are developing. I think it's just taking time for the research to be funded, to use those tools to really try to interrogate the environment and understand, of the millions of possibilities out there, what are the top suspects.

Dr. Diane Reidy-Lagunes:

Yeah, and like you said before, if the latency period could be decades and you need to think about 40 or 50 or 60 years of data to understand that, what is the right type of protocol or research that you can at least try to take an approach at tackling this?

You said a little bit of what you're doing now, which I think could be very exciting as an opportunity. But as we think forward, what type of data or blood samples or something should be collected now, to help us – if we can't answer the question today – for the next generation of folks, to make sure that we don't have this problem 50 years from now?

Dr. Caitlin Murphy:

Right. I think we're at a unique time in history when a lot of the limitations about not having the right samples measured at the right time can be overcome by leveraging existing samples maybe that have been collected for some other purpose.

So for example, I mentioned this study that I've been working on with pregnant women. Back in the 1950s and 60s when that study began, there was no hope of ever sort of using it to understand cancer. But simply because of the amount of time and data that has elapsed, we can now use it for this new purpose.

And there are a lot of other examples out there of similar types of studies of newborns, of birth cohorts, of pregnant women, of children, that maybe started 20 or 30 years ago, but we followed them over time. And so now as they're aging into cancer risk, we can perhaps use some of those samples or interrogate biospecimens that were collected in those studies for this purpose, even though maybe that wasn't on anyone's radar at the time that those studies began.

Dr. Karuna Ganesh:

Another approach is to come at it from looking at the cancers themselves, trying to understand how these cancers develop. One early hypothesis was that maybe the genetics of early onset colon cancer might be different from the genetics of average onset colon cancer. And that hypothesis has been tested, people have sequenced the genomes, and we now know that the genetics are actually pretty much the same. It's the same mutations happening in younger patients and in older patients.

So if it's not the genetics, what's the next hypothesis? One of the things that we've been looking at is: what about the cell in which the mutation actually happens? Are those cells in a transcriptionally different state? Just like how we have the same genome in every cell in our body, but your gut cells are different from your brain cells – that's because they use a different part of the genome and behave differently. In the same way, we can look at: do the cells that the cancer is in, in young patients, behave differently? Do they express different genes than the cells that have the cancer in older patients? We've done some of this kind of work, and one signal that comes through very strongly is that the cells – the same colon cancer cells in young versus old patients – in the younger patients, they have a much stronger signature of injury, of inflammation, which goes back to these questions that Dr. Murphy has raised about environmental exposures. Are we living in a more inflamed environment? And what might be driving that inflammation to happen?

Another approach taken by the UK Biobank has been to look at hundreds of thousands of patients, which they're able to do in large population-based studies, to look at signatures of aging. We know cancer is generally a disease of aging, and they've looked at a number of blood biomarkers of aging. And indeed they find that in patients who have young onset colorectal cancer, as well as some other cancers like breast cancer, they find that the aging signature in the blood is already present in these younger patients. So it's basically suggesting a form of accelerated aging.

So we are learning more about the biology of the underlying cells that are providing a sort of conducive environment for these cancers to grow. What we need is to link the environmental exposures with these cellular consequences that are happening. By understanding the biology of what's changing in the cells, we can design experiments to more rapidly screen a whole bunch of chemicals to really establish the link between the chemical and the cellular consequences that drive the cancers.

Dr. Diane Reidy-Lagunes:

Amazing. Dr. Murphy, you talk about the so-called “usual suspects” when you do your lectures and talk about that being obesity and sedentary lifestyles. But is there anything else – again, recognizing that the data is just not clear yet – that may be contributing to that inflammatory state, if you will, that Karuna is describing?

Dr. Caitlin Murphy:

I think there's an endless number of possibilities, which I know sounds very frustrating in the sense of we're not very close to figuring out what's going on here. I'll offer my own perspective.

When I first started studying colorectal cancer, in particular in young people, I was really convinced that there was one smoking gun risk factor out there that explained everything that we were seeing in terms of the increasing incidence rates. And the same could be said for the rates of many other cancers that are now increasing in young people. But the more time I've spent in this research area, the more I see it is clearly not just one thing. There are probably thousands of things that explain what we're seeing.

I think we need to shift our mindset from the belief that it's obesity, or it's this, or it's that, to really allowing the possibility that it's something we never considered before. We've got to think outside the box a little bit in trying to figure out what it is. So it could be sleep, it could be stress, it could be poverty, it could be environmental chemicals, it could be all of those things. I'd really like to see the research field move forward with these discovery-based approaches rather than testing one hypothesis at a time.

Dr. Karuna Ganesh:

Dr. Murphy, could you tell us more about the new ways to look at the exposures people have?

Dr. Caitlin Murphy:

Sure. I am inspired by this new concept called the exposome. This is a complement to the genome that contains all of our genes, but the exposome is meant to represent all of our exposure. So the cumulative impact of the environment on our health lies in this thing called the exposome.

Biochemists have developed new tools to interrogate the exposome, identify thousands of signals at once, and annotate those signals as being environmental chemicals or some other thing in the environment. And that is one, I think, promising approach to trying to do more discovery-based work. What can we see all at once – sort of this 10,000-foot view, 10,000 chemicals in a sample – versus just one thing at a time?

Dr. Diane Reidy-Lagunes:

Yeah. Sounds like artificial intelligence will hopefully help us here.

Dr. Caitlin Murphy:

Certainly, yeah. Data science is an important piece of that, right? Because we have to have some computational tools to make sense of the thousands of signals we might be getting out of a blood sample. So it's really a team science effort: chemists, epidemiologists, data scientists, oncologists. We traditionally work alone in silos, and now we’re really thinking about opportunities to work together to apply our skills to these new ways of tackling the challenge.

Dr. Diane Reidy-Lagunes:

Absolutely. So who's responsible for being a governing body for this? It just seems like somebody should be watching to make sure that 50 years from now we don’t have something else that’s causing a major health crisis.

Dr. Caitlin Murphy:

Yeah, I wish I knew the answer to that because I'd go and find that person and hold them responsible. I think from a scientific perspective as researchers, our responsibility is to push the envelope to the extent that we can. We're under pressures in terms of having to get things funded, having reviewers review things in a certain mindset. But I think the more that we, again, push the envelope and change the paradigm, we might get a little bit closer to being able to fund some of these more non-traditional types of studies to answer questions.

I think we need to be careful too of not holding individual people responsible for monitoring whatever exposures might be out there. As an example not related to cancer, there was a study a couple of years ago that showed that phthalates – these are in cosmetic personal care products – are related to risk of preterm birth. And the conclusion of this paper was that pregnant women just needed to read the labels of all their personal care products. But in Europe and many other countries, these chemicals are not included in those products. So I just want to be careful that even if we do discover, let's say, a certain chemical is related to these cancers, that we don't then put the onus back on the individual person to monitor their risk, and we really advocate for policy and system-level change.

Dr. Karuna Ganesh:

I could add to that. Back in the 1960s, a similar debate was underway globally about why there was this huge increase in lung cancer. And there was a similar thing: “Oh, there's so much pollution,” non-specific stuff that could be toxins, chemicals, etc. and nobody really could say there's one smoking gun. And yet there was, and it was actually an epidemiologist at Oxford, Richard Doyle, who came up with this new study design called the Cohort Study, which allowed us to definitively establish that smoking causes lung cancer. And this led of course to a multidimensional policy initiative where people were actively discouraged from smoking, which was of course a widespread population in that time, as well as education and regulation of industry and so on.

And to second Dr. Murphy's point, it's not something that individuals alone can be held responsible for. At this time we don't really understand the reasons, but as we've already discussed, it's not clearly obesity, it's not clearly something that you ate or didn't eat, or some behavior that you did or did not do.

As somebody who sees a lot of patients with early onset colorectal cancer, this is a question that my patients often ask me: “What did I do wrong, doctor?” And you didn't do anything wrong. It's unfortunate there's something that we don't know. We are all working really hard to figure out what it is so we can prevent this from happening, but it's not something that any one person did or did not do. So please, people should just live their lives.

Dr. Diane Reidy-Lagunes:

Yeah, I want to underscore that as well. As I said earlier, I have marathon runners unfortunately in my clinic with stage 4 colorectal cancer. So we often say it's not anything you did or didn't do, it's much more complicated.

Do you think from a medical professional perspective, this rising incidence is going to change how we think about cancer screening and treatment in the future?

Dr. Karuna Ganesh:

Absolutely. I think it's already changing that. Take colonoscopies, which are done to detect precancerous tumors before they turn into cancer and cut them out. We used to do colonoscopies starting at age 50, but recently the screening task force guidelines have changed that recommendation to start colonoscopy screenings at age 45, and even younger if you have a close relative who has a cancer diagnosis like breast cancer or colorectal cancer, in which case you should be getting screened at least 10 to 15 years younger than their age of diagnosis. This will also evolve over time.

With any screening guidelines, of course, we need a couple of different parameters to be met. One is, we need to know that there's a test that can be done that can detect an early lesion, such that something can be done about it. So you do mammograms so that you can detect precancerous tumors and cut them out before they have a chance to turn into cancer, and same thing for colonoscopies.

And we need enough time between the detection of that precancerous tumor and the cancer actually developing so that we have time to do something about that. I think understanding that is going to require more of an understanding of the biology of these cancers. What is actually driving them? What does it mean that they're more inflamed? Does this mean that they develop faster? Is there going to be an adequate screening interval, or do we need to have some novel approach or novel technology to do this kind of cancer screening? So there's a lot of unanswered questions, at the moment.

But certainly, if anyone has any symptoms, I think the real thing right now is to be vigilant. If you're a young person with rectal bleeding that doesn't go away in a day or two, please go see your doctor and ask to have a colonoscopy.

Dr. Diane Reidy-Lagunes:

Yeah, absolutely. And for mammograms, the screening went from 50 to 40 in part because of the rise of early-stage breast cancer. So hopefully we can detect earlier for that with this change in recommendation. And there are things that we can do to prevent cancers, like the HPV vaccine. Certainly the number of head and neck cancer and cervical cancers have gone down dramatically, thankfully, because of that intervention. So there are overall things that we can and have done to ensure that we can prevent or detect earlier with these screenings.

Dr. Karuna Ganesh:

Absolutely.

Dr. Diane Reidy-Lagunes:

Karuna, Caitlin, thank you so much for spending time with us today. We learned a lot as always.

Dr. Caitlin Murphy:

Thank you.

Dr. Karuna Ganesh:

Thank you.

Dr. Diane Reidy-Lagunes:

Thank you for listening to Cancer Straight Talk from Memorial Sloan Kettering Cancer Center. For more information or to send us your questions, please visit us at mskcc.org/podcast. Help others find this helpful resource by rating and reviewing it on Apple Podcasts or wherever you listen. Any products mentioned on the show are not official endorsements by Memorial Sloan Kettering. These episodes are for you but are not intended to be a medical substitute. Please remember to consult your doctor with any questions you have regarding medical conditions. I'm Dr. Diane Reidy-Lagunes. Onward and upward.