Is there a link between cancer and heart disease? | Nicholas Leeper

0:00Hey listeners, this is Ted Health. I'm Dr. Shoshana Ungerleiter. On today's show, cardiologist Nicholas Leeper explores the link between the world's two leading causes of death, heart disease and cancer. He makes a strong case for breaking down the traditional silos in science that stop scientists from seeing similar links sooner. And after, I'll share my own recent experience facing illness and how my father's cancer diagnosis may be saving my life.

0:36In two decades of practicing medicine, I've encountered a wide number of medical diagnoses. You see, it turns out that there are more than 60 ,000 different medical diagnoses that you can list on a patient's chart that you can actually be diagnosed with a burn injury when your water skis catch on fire. There are also codes if you need surgery after being bitten by a pig, hit by a spacecraft stabbed while crocheting or my favorite due to extreme problems with your in-laws. But the best of all has got to be the code for getting sucked into a jet engine. And the reason that I like this one is because this is not the code for the first time this happens but for the subsequent encounter.

1:25So there must be people on this earth that have been sucked into a jet engine twice.

1:32But I think, you know, kidding aside, we have to recognize that every last one of us in this room is most likely to die of only one of two diagnoses. And these, of course, are either cancer or cardiovascular disease. This speaks to the incredible public health importance of these two diseases and the urgent unmet medical need to develop new therapies directed against them. A lot of people are not surprised that these two diseases claim so many lives. After all, they are very different biologically, they have different risk factors, and they affect very different patient populations. But for the next 15 minutes or so, I would like to propose a different hypothesis, that perhaps they actually have quite a lot in common.

2:20And even more importantly, I would like to suggest that if we think about them this way, we might be able to develop new therapies that could treat both diseases at the same time. So before I tell you why I believe this hypothesis, let me lay out the counter arguments against it. I think many people would say that the old man who smoked cigarettes his whole life and has a heart attack shares very little in common with a young person who develops colon cancer out of the blue. But we now know that the risk factors for these diseases have significant overlap, and the things that cause one disease can also put you at risk for the other.

2:59Well, that may be true, but we know that genetically these diseases couldn't be more different. I'm sure many of you have heard about these cancer genes that can be mutated in families that could put both mother and daughter at risk for breast cancer. We know that those genes have nothing to do with heart attack. And that's true also, but I would point out that those genes were discovered decades ago, before the Human Genome Project and before we could scan all 3 billion base pairs at the same time. And when we do this for patients having heart attack, we find that the top hotspot for having a heart attack is located on chromosome 9.

3:38And what shocked the world when this paper was first published was that this genetic locus has nothing to do with smoking or cholesterol or diabetes, but actually seems to control a well-known cancer gene that's mutated in patients with melanoma, brain cancer, lung cancer, etc. And so for decades, we've been focusing on the traditional cardiac risk factors, but the genetics now tell us that the most important factor may actually have to do with a well-known cancer gene instead. Well, that's an interesting observation, but we know that if you look under the microscope at these two diseases, they couldn't be more different.

4:18When I was in medical school, I was taught that cancer is really just about cells dividing too quickly. And you can imagine this lung tumor growing over time and taking over the lung. And that this has nothing to do with what happens in heart disease, which is a problem that I was taught was due to the buildup of cholesterol that can ultimately lead to the blockage of an artery and the heart attack or a stroke. And to be sure, both of these biological processes are critically important, but I would point out that the modern-day textbook of these diseases is getting harder and harder to tell apart.

4:55We now know that both of these conditions are dominated by the influx of inflammatory cells and immune cells and abnormal blood vessels and even stem cells. And so maybe the textbooks that I used are out of date. Well, at this point, you might say these are interesting observations, but is there any clinical data which would suggest that patients with one disease are actually at higher risk of the other. It turns out that investigators, both in Asia and Europe, have now started to test this hypothesis. And just last year, a very important article was published out of Germany, where they looked at more than 100 ,000 individuals with congestive heart failure.

5:36And they found that these people were at much higher risk of developing cancer. This is really interesting and suggests to me that, indeed, having one disease may put you at risk of the other. But this also raises a very important scientific principle, that association is not the same as causation. And if you wanted to test that hypothesis, you would have to do an experiment where you took a healthy individual and then intentionally gave them a heart attack. You'd have to let some time go by to see what changes occur throughout the body, and then you could determine if their rate of cancer was higher or vice versa if their rate of heart disease was higher.

6:18Now, obviously, we can't do this type of an experiment in human beings. This would be unethical. But this type of an experiment is done in research laboratories every day around the world in mouse models of human disease. Just last year, two very important studies were published where investigators took healthy mice and then implanted small tumors underneath their skin. They looked at the rate at which these cancers would grow over time. And what they found in both studies was that the mice who had heart disease had much higher rates of cancer. And what was fascinating to me was that they were able to confirm these findings across a wide range of tumors, suggesting to me that really the presence of heart disease is sufficient to accelerate cancer growth.

7:07so having heard all this the natural question is whether we can do anything about this so outside of my work at stanford one of my volunteer roles is with the american heart association and one of our public health initiatives is called life simple seven we try to get patients with a history of heart disease to control these very simple and straightforward risk factors like exercise, cholesterol, and diet. The idea here is that if you can control these, you should be able to lower your risk of having additional cardiovascular events. This is now pretty widely accepted. But what's fascinating to me is that a group of investigators have now looked at the association with these risk factors and cancer.

7:52And in a study with more than 10 ,000 individuals who were followed for almost two decades, they found the people who had optimal control of all their risk factors had a pretty low rate of developing cancer. But for each risk factor which fell out of control, the risk of malignancy went up. So this suggests to me that, in fact, if we want to control cancer, we might start by controlling our cardiac risk profile. So this is fine, and we continue to encourage our patients to do this. but the reality is that even if I had a magic wand and could somehow optimally control everybody's risk factors, we know that we would still be dealing with both number one and number two causes of death worldwide.

8:41This tells us that we need to find new therapies that could treat or even prevent these conditions in the first place. Now our laboratory chooses to do this with an unbiased genetics approach. We take biopsies from patients with or without a wide variety of tumors or with and without cardiovascular disease. And instead of looking at one gene at a time, we scan the whole genome and look at the expression of all 20 ,000 genes. And when you acquire enough samples, you can begin to identify patterns of those genes which are bad for cancer versus those that protect against it, and do the same type of an experiment to find those things that will accelerate or prevent against cardiovascular disease.

9:26Now, I think the clever part of this approach is to integrate these and to run these analyses simultaneously. Now, our group has run these analyses on several thousand individuals. This work is still underway, but so far we've identified a list of about three dozen pathways that we do think should be prioritized. Now, time will tell if these work, if all of them work, if some, if any of them work. We just don't know. But I do want to show you a couple of examples that would suggest that we're on the right path. One of the factors we found relates to inflammation. And we often think of inflammation as being bad, but in reality, this is a process that our body evolved to help us recover from injury or to mount a fever to fight off an infection.

10:15But of course, there are always times where our body has too much of something. In this case, there's a rare genetic syndrome where children can be born with overactive inflammation and they can have recurrent episodes of high fevers and rashes and other neurocognitive and developmental delays. Now, in a triumph of science, investigators have pinpointed the exact molecule responsible for this and they developed a drug that can block it. These children who have these rashes that I mentioned before can have a relatively remarkable improvement on these drugs and almost get back to a normal quality of life.

10:54But relevant to today's talk, it turns out that there are a group of cardiologists who for decades have hypothesized that these same inflammatory factors may also be driving heart disease. They were able to convince the company that makes this drug to do a trial to look at the effect of this medicine in patients who had had a heart attack or a stroke in the past. And really, it was no surprise to many of us when the results of this trial were published, and they showed that, in fact, compared to a placebo, that this medicine could prevent recurrent cardiovascular events. But our algorithms predict that this drug should not only help prevent heart disease, but also should be able to prevent cancer.

11:37And so this particular article gained a lot of attention because when they unblinded their results, the investigators were shocked to find that not only were the patients having fewer heart attacks, but they were having a much lower rate of developing lung cancer and a much lower rate of even dying from cancer. In fact, these results were so surprising and powerful that I understand the company that makes this drug is now pivoting and prioritizing this as a cancer drug because the effects were so significant. We don't yet know if any of these other pathways will have the same type of success. But what we do know for sure is a lesson that Galileo taught us almost four centuries ago, and that there is no such thing as settled science.

12:24We must challenge dogma. We must break down traditional silos, because if we do, we may no longer be powerless against these leading killers, but may in fact find ways to treat the world's two leading killers. Thank you.

12:45Hey listeners, it's Dr. Shoshana again. Nicholas Leeper's talk about discovering the links between heart disease and cancer really struck a chord with me. You see, in late June, I got a phone call from my 73-year-old father. He said, I have some bad news. Hearing that tone in his voice, my heart sank immediately. My father had been having pain in his belly for a few months, so he got it checked out, and the doctors found a mass in his pancreas. As a daughter, I was worried. I suspected that my dad had cancer because it runs in our family. My grandfather, grandmother, and uncle, all on my dad's side, died of various cancers.

13:33And as a doctor of internal medicine, I knew this was very likely terrible news. Because pancreatic cancer is often not detected until very late, it's extremely difficult to treat. And the median survival rate in the advanced stage is only a handful of months. We all braced ourselves for the worse. At my dad's first visit to the oncologist, we learned that things were worse than we'd imagined. The disease was at stage four and had spread to his liver. My heart sank again. But there was some hope. The oncologist explained that some late-stage patients with pancreatic cancer were outliving the typical grim prognosis.

14:21These patients had taken a new class of medicines called PARP inhibitors. PARP inhibitors target cancer cells by stopping them from repairing themselves. These drugs offer a potential effective treatment option in people with advanced pancreatic cancer and a BRCA, or BRCA gene mutation, which is short for breast cancer. This is the same genetic mutation that Angelina Jolie made famous after sharing her story publicly back in 2013. All humans have two copies of BRCA1 and BRCA2 genes. They help prevent certain cancers. And if there's a mutation in one of the BRCA genes, the resulting proteins may not do their job repairing DNA as well, causing a predisposition to certain cancers.

15:10In Nicholas Leeper's talk, he theorized that genes like these could have a link to heart disease. We don't know yet, but we do know that in the general population, About 1 in 400 people have BRCA mutations, and they run in families. Since none of the cancer in my family was breast or ovarian, I was pretty sure it didn't run in mine. Or so I thought. It's a myth that BRCA is only about breast cancer or ovarian cancer. BRCA mutations can lead to several kinds of cancers. After talking to a genetic counselor, I learned that the chances of my father carrying it was even higher. For Ashkenazi Jews, about one out of 40 people are affected, which is our family heritage.

15:58And if you have the mutation, you have a 50 % chance of passing it on to each of your children. I felt a cold chill when I learned this, so I was tested too. I waited three weeks, feeling pretty certain that I would be in the clear. So when the results came back positive for a BRCA2 mutation for both my father and me, we were surprised The good news was that my dad was now eligible for the new treatment It was a strong ray of hope that we might be together for many more good years The news for me certainly wasn't good But the silver lining in my dad's terminal disease is that he very well might be saving my life I'm now on a mission to spread the word that BRCA is not just found in families with breast and ovarian cancer.

16:51These cancers aren't in mine. I also learned that not all doctors know that this genetic mutation is associated with a higher risk of pancreatic, prostate, and other forms of cancer. I sure didn't, and neither did my doctor. It's also important to ask your doctor and even educate them about genetic counseling and screening, just as I did. I hope that my father's story, which is now part of my own, can help the almost 1 million people in the U.S. who have the BRCA mutation, at least 80 % of whom don't know it. And how do I feel about my diagnosis? well, if I wasn't a doctor, I probably would have been more upset by the news.

17:37But I know there are evidence-based options for how to proceed, from preventative surgery to regular screenings to lower my lifetime risk of cancer. As strange as it sounds, I actually feel grateful and empowered by the diagnosis. With my strong family history of cancer, I always just assumed I would get it too. but now I'm not simply waiting for bad news. I know my risk and I can take action. I can decide what I want to do with this information rather than just hoping to be lucky. I'm making choices that align with my own goals and values for living what I hope will be a very long and full life.

18:27Thanks so much for listening today. This episode was produced by Joanne DeLuna and fact-checked by Ted. And special thanks to Anna Phelan, Maria Lajas, Michelle Quint, Grace Rubenstein, and Colin Helms. I'm Dr. Shoshana Ungerleiter. Stay well, and I'll talk to you next week.