Preventing Cancer: Thwarting a Disease that Affects 1 in 3 Americans
Chances are you or someone you love has been affected by cancer. In fact, more than one in three Americans will develop cancer in their lifetime. This is a disease that takes many different forms, has innumerous causes both known and unknown and affects people in a variety of ways.
In this episode, we talk to four experts from the University of Michigan School of Public Health to learn about their research on cancer, and what they're doing to try and prevent it.
Be sure to follow us at @umichsph on Twitter, Instagram, and Facebook, so you can share your perspectives on the issues we discussed, learn more from Michigan Public Health experts, and share episodes of the podcast with your friends on social media.
00:02 Speaker 1: I'm a cancer molecular epidemiologist and I am very interested in tumors and what a tumor can tell us about why a person got the cancer, what led to the development of the cancer and what that tumor tells us about how we can treat the cancer and whether or not that person is going to survive. And it's interesting because tumors develop over decades. And for most people, it takes decades of exposures and decisions and lifestyle that is associated with how that tumor grows and develops. I like to think of this as like the pyramids of Giza in Egypt. So when I was a kid I loved reading about the pyramids. And what was most interesting to me were the stories where archeologists would go and they'd look at the pyramids. And, they would look at whether or not they were lines in the ground, and they could say, "They dragged the bricks across here," or where the lakes were that were leading up to the pyramids, and maybe they floated the bricks and how did they lift them?
01:03 S1: And I feel like that's what I do when I look at a tumor. I look at the structure of the tumor and the different genetic changes in it, and the way that it's in your organ and how it sits and how it behaves, and I think, how does that tell us why a person got the cancer, and what exposures led to it. And looking at these worldwide where exposures are dramatically different in low-income countries, in middle, and in high and dramatically different in urban and rural populations I feel like that tumor can tell you so much about this. And to me, it's the most fascinating part of studying cancer.
01:38 Speaker 2: Chances are you or someone you love has been affected by cancer. In fact, more than one in three Americans will develop cancer in their lifetime. This is a disease that takes many different forms, has innumerous causes both known and unknown and affects people in a variety of ways. Today we're talking to four experts from the University of Michigan School of Public Health to learn about their research on cancer, and what they're doing to try and prevent it.
02:07 S2: Hello and welcome to "Population Healthy" a podcast from the University of Michigan School of Public Health. Join us as we dig into important public health topics, stuff that affects the health of all of us, at a population level. From the microscopic to the macro-economic, the social to the environmental, from neighborhoods to cities, states to countries and around the world.
02:40 S2: We can learn a lot about the pervasiveness of cancer and what may be working to slow it down by learning about the numbers behind the disease. Mousumi Banerjee is a research professor in the Department of Biostatistics, at the University of Michigan School of Public Health and a member of the University of Michigan, Rogel Cancer Center.
03:00 Banerjee: Statistics is I believe crucial in all areas of cancer research. Cancer research spans a wide range of areas including the basic sciences, clinical research, supportive care, population health and statistics provides a framework for doing evidence-based medicine across this entire spectrum starting from diagnosis to treatment decisions, cost-effective health care delivery and outcomes, you name it. It provides a foundation for scientific decision making. In 2019, it is estimated that roughly about 1.7 million cancers will be diagnosed in the United States which is more than 4800 cases per day. A daunting number.
03:50 Banerjee: Cancer is the second leading cause of death in the United States after heart disease for both men and women. So, it's a huge public health problem. Among men, the most common cancers diagnosed are prostate, lung and colorectal and together these three account for almost 42% of all cases in men. Prostate cancer alone, accounting for nearly one in five new cases. So for women, the three most common cancers are breast, lung and colorectal and together these three account for one half of all cases, with breast cancer alone accounting for 30% of the new cases.
04:37 Banerjee: These cancers also account for the greatest numbers of cancer deaths. These are all very, very depressing statistics but there is good news and the good news is that during the most recent decade of data that's available going from 2006 to 2015, the rate of new cancer diagnosis has decreased by about 2% per year in men and stayed about the same in women. So the death rate has actually declined steadily over the past 25 years. As of 2016, the cancer death rate for men and women combined has fallen almost like 27% from its peak in 1991.
05:24 Banerjee: According to a recent study by the American Cancer Society, at least four out of 10 newly diagnosed cancers in the US, are potentially avoidable. It's a big number, and this includes 19% that are caused by smoking and 18% that are caused by a combination of things like excess body weight, physical inactivity, excess alcohol consumption and poor nutrition. So, these are all modifiable. Certain cancers that are caused by infectious agents such as the HPV virus, the Hepatitis C virus, the H. Pylori, these could be prevented through for example behavioral changes, vaccination, treatment of the infection and so on.
06:10 Banerjee: Another example, skin cancers. More than 5 million skin cancer cases that are diagnosed annually, could be prevented by protecting skin from excessive sun exposure and not using indoor tanning devices. Screening can help prevent colorectal and cervical cancers by allowing for the detection and removal of precancerous lesions and screening also has the opportunity to detect some of the cancers early, and we all know that when diagnosed early mortality for cancer, such as breast, colon, rectum, cervix, lung cancer can be improved. And I think in addition, a heightened awareness of changes in certain parts of the body, such as breast, skin, mouth, the eyes, may also result in the early detection of cancer. So together all of these things could potentially help us in some of these prevention efforts.
07:16 S2: With a disease as varied and complex as cancer, prevention takes many different forms. The goal of researchers is to identify the right prevention at the right time, that can mean many different things, from country to country.
07:29 Rozek: So my name is Laura Rozek. I am an associate professor of Environmental Health Sciences Nutrition and Global Public Health here at the University of Michigan School of Public Health. Most of my work looks at people who have cancer and at risk factors that may have given them the cancer and how those might predict survival from cancer. We can broadly separate cancer prevention into three categories, there's primary prevention, secondary prevention and tertiary prevention. Primary prevention aims to stop the cancer before it even occurs, before there's any indication that there is cancer and this is the cornerstone of public health and the role of public health in cancer prevention. A lot of these strategies are strategies that we do every day here in the United States and worldwide, so vaccination for the Hepatitis virus and HPV viruses is a form of primary prevention because it stops the cancer before it occurs.
08:24 Rozek: Tobacco laws and tobacco cessation programs, these are helpful in preventing tobacco-related cancers. Secondary prevention is an attempt to diagnose cancer as early as possible in order to have the largest impact on survival. And this is where screening programs come into play. The screening programs we often think of that are most helpful with cancer are cervical cancer screening programs like PAP smears, we also have screening programs for colorectal cancer and for breast cancer. In high-income countries, these are really widespread, so most people have a colonoscopy and right now, breast cancer screening programs are readily available in most high-income countries, but they aren't in lower-income countries. And some of the work we've done have looked at ways that we can make cervical cancer screening more accessible to people by using any kind of self-sampling method to look for HPV, which is the virus that's ideologically associated with cervical cancer.
09:22 Rozek: There are all sorts of ways we're trying to mobilize colorectal cancer screening programs, so these can be done in the field and we can identify cancer earlier. Now tertiary programs are associated with your survival and health effects after you're diagnosed. With tertiary prevention, we're really concerned with how we can give people the best treatment for their cancer where they're going to have the longest survival and the best quality of life and this is where precision health can benefit us, especially in western countries, again, where we are able to look really significantly into some of these tumor and say, "This is the best type of therapy for this tumor." These, of course, are not readily available throughout the United States or throughout the world, where people who are of low income or people in lower middle income countries are much less likely to have these kinds of therapies available because it's very expensive to treat cancer and we know that.
10:12 Rozek: And it's also expensive because we need to have the right type of physicians who are available who can have a knowledge base and the ability to treat these cancers. So much of my work is in a global setting and what I've been struck by is that the different countries that we go to have not only different rates of different types of cancers, but the actual cancers are different because for example, when we think of something like breast cancer, a lot of people think that breast cancer is one entity, it's just breast cancer, but there's many different types. There's hormone receptor positive, hormone receptor negative, when you get your breast cancer in life is actually usually indicative of how severe the cancer is going to be. If you have it earlier in life, it's often a more sever cancer. These are cancers we see more often in lower middle income countries.
11:00 Rozek: Now, how this can inform cancer in Western populations is that, and the United States is a perfect example, we are a mix of many different types of people here. And again, this is something we celebrate every day, but we do know that cancer rates are different based on your ancestry. Now as we have looked across populations and across the African Diaspora, we've noticed that areas of Africa from which African-American women in the United States came, so, Ghana, for example, they are much more likely to have much more aggressive breast cancer subtypes. But when we look at East Africa, for example, Ethiopia, there are actually much less likely to have these aggressive cancer subtypes indicating that there's probably something that is uniquely genetic or something about the biology of these women and these tumors that's just inherently different, and that helps us inform how we can treat these cancers and to look at there to see maybe there's ways that these cancers can inform precision medicine specific to the African-American population.
12:01 Rozek: We know that one of the cancers that's increasing in the united States is a young onset colorectal cancer, and this increase is actually greatest in African-American men and women. We have tumors from Ethiopia, we have tumors from Ghana and we have tumors from Detroit and so we are looking across the genetic differences in these tumors to see maybe there's something that's just ancestrally similar with these tumors, maybe we can identify navel changes in these tumors, that can tell us, "There's a better way to treat this, there is a better way to prevent this." And because with both breast cancer and with colorectal cancer, we can change the screening guidelines. We can say if you are African-American, you might want a screen at 40 for colorectal cancer. There might be ways that we can change this where the global biology of the tumors can inform this. And again, it's really exciting and it's really exciting research to think about how this can inform precision medicine worldwide.
13:00 Rozek: So we often I don't think give enough credit for where we're doing a lot of really good public health successes. And one of them is cervical cancer in western countries, where the widespread availability of Pap screening has led to really just incredible decreases in the incidence of cervical cancer. And that, in conjunction now with widespread availability of the HPV vaccine, we can see in front of us, we can see that we can end cervical cancer definitely in Western countries, and likely worldwide. And this is an area of emphasis for the World Health Organization. Now where HPV vaccine is not readily available, so in many lower middle income countries, and definitely in low-income countries, but the knowledge is there. And we've done some work in Ethiopia and in Thailand and we've tested ways that we can make cervical cancer screening more accessible to populations that either may not have PAP screening available or something called VIA, which is another way that they can do a visual test, for cervical cancer or they just might not wanna do it just because of cultural reasons.
14:04 Rozek: So we've looked at ways that women can self-test because if a woman knows that she's HPV positive she is much more likely to develop cervical cancer, and she can be referred for more screening, and the woman is more likely to do it because we can say to this woman, "You have a virus that means you can get cancer." Because a lot of our studies ask women what is their knowledge-base on cancer? And even in low-income countries, they know. They know, that things are available and we found through our studies that they're willing to get tested. Oftentimes, it is an issue, where they wanna do it in the way where they're comfortable and where their entire family is comfortable with it, and that they're willing to do what it takes to not get cancer.
14:43 Rozek: Childhood cancer, detection and treatment is another major emphasis area for the World Health Organization. That's because we're realizing that the earlier we treat childhood cancer, and the better we're able to target the therapy, the fewer late life health effects because a lot of childhood cancers can be treated very efficiently, but the quality of life and some of the effects during this very critical window of development can lead to these long-lasting issues in children as they move through decades of life.
15:13 Rozek: In lower middle income countries children can be diagnosed late for a number of reasons. One of them is just not having the availability of a cancer hospital or a treatment center where they're able to diagnose this. And we do some work in Indonesia with Dharmais Cancer Center where they have a destination program for childhood cancer, but in a country with 17,000 islands where they have significant travel obstacles to get to the hospital, often by the time they know they have cancer, it's actually quite late. Worldwide policies that address cancer and cancer incidents are again the bread and butter of public health, because public health can make population level differences that will affect decades of cancer incidents.
15:54 Rozek: Of course, the most common example is tobacco where our policies on tobacco taxation, and tobacco laws limiting when and who could buy cigarettes have played a major role in decreasing tobacco use in many countries, not only high-income countries. And I'll point out here Thailand which has historically had some of the strongest tobacco laws in the world, the rates of tobacco smoking in Thailand are well below the rest of Southeast Asia. And they've been progressive and they've been effective.
16:26 Rozek: And that'll be interesting to see what happens as we're watching more of these policy-based solutions to public health come into play. We're starting to recognize that alcohol may play a stronger role than previously thought in the development of cancer, and the WHO is reacting to this by following up their framework convention on tobacco control with a similar convention on alcohol use worldwide. And these laws again, are pivotal for public health and a variety of diseases. But just pointing out here, that even if we don't see the direct relationship between these laws and cancer, that they actually have a very, very direct relationship because the more healthy a population, the less likely they are to have high rates of cancer and we see that just about everywhere.
17:15 S2: One of the policies that has been particularly effective in preventing cancer, both in the US and in other countries across the globe is tobacco control. But even with successes in tobacco control lung cancer remains a leading cause of death throughout the world.
17:31 Meza: Hi, my name is Rafael Meza, I'm associate professor of Epidemiology and Global Health at the University of Michigan School of Public Health and co-leader of Cancer Epidemiology and Prevention of the University of Michigan Rogel Cancer Center. Lung cancer is quite common, unfortunately, it's actually the number two cancer in both men and women in the US. Actually more people die of lung cancer in the US than from breast, prostate, and colon cancer combined, and globally is number one, in terms of incidents, as well as mortality. We actually are now seeing important declines in many places, and in many countries, particularly in developed countries like the US or England and others where really, the majority of lung cancers that we see now are due to smoking. As smoking has come down in many places thanks to tobacco control and just thanks to the awareness that smoking is bad for your health, and as a consequence lung cancer which increased a lot in the past century now is coming down. But unfortunately that's not uniform. There are countries and places where for instance smoking is not decreasing, may actually be increasing.
18:46 Meza: There are other risk factors of lung cancer besides smoking. So for instance, miners who might be exposed to asbestos or arsenic or radon gas tend to have higher rates of lung cancer. Environmental radon gas exposures and residential radon gas exposures is one important risk factor. So for instance, that's why it's important that if you live in an area where there is environmental radon, you would test your house and if there is radon gas present that you would treat it. Second-hand smoke, if you don't smoke but you are next to people who smoke, that will also increase your risk, and it's related but for instance, having chronic obstructive pulmonary disease, so like emphysema or chronic bronchitis is a risk factor for lung cancer.
19:37 Meza: The lung cancer screening is a relatively new modality of cancer screening. It was actually recommended at the end of 2013 and 2014, not for everybody, but for a subset of current and former smokers, between the ages of 55 and 77, according to CMS or 80 according to the US Preventive Services Task Force. And smokers who have smoked at least, what we call 30 pack years. If someone smokes one pack of cigarettes a day for a year, that's one pack years. So, it's really for for instance smokers who have been smoking for at least 30 years, one pack a day, or any other combinations, and for those former smokers that they haven't quit for more than 15 years.
20:21 Meza: Slowly, it has been implemented in the US and it's going, but it's certainly not yet at levels of other cancer screenings, such as mammography or colorectal cancer screening, that's one of the ongoing challenges, to disseminate the knowledge that there's this test and if you're a current or former smoker, you might qualify and you might be recommended to do it and, of course, getting people to think about it, if it might be something that would be good for them. Lung cancer screening is able to detect lung cancers earlier, usually, lung cancer presents itself very late, when you have symptoms is when you might have a cancer that's already stage 3 or stage 4. And unfortunately, the prognosis for those cancers is pretty bad. That's where lung cancer screening comes, where maybe through a CT scan, you'll be able to find a nodule and find it at a time when it is still treatable, so, maybe, stage one.
21:12 Meza: Everyone who has lungs is at risk of lung cancer and, of course, we know that those who smoke are at the highest risk of lung cancer, but even among the whole population, there are groups who might have certain preconditions or predispositions. If you have cases of lung cancer in your family, you would be at highest risk. Unfortunately, African-Americans in the US are a group that seems to be particularly affected by lung cancer and particularly certain types and they have been identified to be at higher risk for instance, than comparable folks from other racial groups, even if they smoke the same level. Lung cancer is a disease that has a lot of stigma. Unfortunately, smokers tend to be pointed at and sometimes consciously or even unconsciously, even blamed for their disease. And I think that has been one of the issues with lung cancer screening.
22:06 Meza: Unfortunately, there isn't a lot of advocates out there fighting to help people get screened or telling people to get screened. There isn't much of a I guess community who's organizing raises or events so people can learn about it. So, I think we really need a lot of help getting the word out and making sure that smokers, of course, former smokers, and everybody know that if someone gets lung cancer it's not their fault. There's many factors that come into play for people getting a disease like lung cancer. And in the end, it doesn't matter who you are, you should get the help and the resources that you need, and in this particular case, it doesn't matter if you are still smoking or you used to be smoking.
22:50 Meza: So, for people that have been smoking for a long time, there is nothing better to reduce the risk of lung cancer than to stop smoking. So, even if you've smoked for a long time, when you quit, immediately, you start collecting benefits in reducing your cardiovascular disease, improving your health, and your physical capability, and after a few years, your risk, for instance, for something like lung cancer, is gonna start decreasing. It will not get to the point of being similar that of a never smoker, but it will go down.
23:29 S2: Smoking is just one common risk factor for cancer, another is obesity, which actually increases your risk for many types of cancers.
23:38 Colacino: I'm Justin Colacino, I'm an assistant professor of Environmental Health Sciences, and also assistant professor of Nutritional Sciences here at the University of Michigan School of Public Health. My lab is interested in studying how diet and environment interact and cause cancer. Obesity is defined by looking at a ratio of an individual's height and weight, using a method we call the body mass index. So the body mass index is calculated as an individual's weight in kilograms, divided by their height in meters squared. And so a body mass index of greater than 25 but less than 30 is considered overweight, a body mass index of greater than 30 is considered obese. Researchers and doctors will also use other methods to calculate obesity, they'll look at things like waist-to-hip ratio or sometimes skin full thickness or total body fat as well. We know about the links between obesity and cancer from various methods, from human population studies, as well as animal studies, so really, we know that obesity is a huge public health problem, first of all.
24:36 Colacino: The Centers for Disease Control estimates that about 70% of the US population are either overweight or obese, which has lead to a lot of studies linking obesity and cancer. And so, how we do this in a public health setting, is with cohort studies, where we follow a group of people over time, and we look to see who gets cancer, and then we can look back at previous characteristics and compare are the individuals that are more likely to get cancer those who are more obese at baseline, or not? So, we know that obesity is related to increased risk of a number of different cancers, and these are some of the most common cancers, like breast cancer and colon cancer, and it's also related to some of the most aggressive cancers that are hardest to treat like gallbladder cancer and pancreatic cancer.
25:20 Colacino: What we're trying to figure out is, can obesity itself, cause cancer? Right? And so, a lot of these epidemiological studies and animal studies have pointed to obesity being a risk factor for up to 17 different cancers. And so, researchers are starting to understand how obesity might cause cancer. And there's a number of different ways or hypotheses that researchers think that obesity might increase cancer risk. And so, one of them is through inflammation. Obese individuals, if we look at their blood, they have higher levels of sort of inflammatory factors than lean individuals, and we can also do studies where we look at adipose tissue itself in obese versus lean individuals, and when we look at that adipose tissue from obese individuals, we see infiltration of a lot of different immune cells that kick-off all of these really potent inflammatory factors and what we're learning now is that those inflammatory factors can promote the growth of tumors.
26:09 Banerjee: So that's one way that obesity might be able to cause cancer, we also know that adipose tissue itself can promote the generation of different hormones like estrogen and we know that estrogen is really important for the development of cancers like breast cancer or endometrial cancer. Adipose tissue is the body's fat tissue and usually it's made up of what we call adipocytes, those are our fat cells and there's also a bunch of other cells in there, there are some immune cells in there, there are some cells like blood vessels in there and all of this comes together to make that fat tissue and that's what we call adipose tissue.
26:39 Colacino: We know that obesity is also associated with high levels of insulin and a similar growth factor called insulin-like growth factor. These are really important signals that tell cells that they need to grow and they've been linked to an increased risk of cancer at multiple sites. And then fat tissues themselves also produce their own signaling molecules which we call adipokines, one of these common ones is called leptin and we know that increased levels of leptin also lead to increased amounts of cellular proliferation. So there's multiple ways that obesity we think might be mechanistically linked to the development of cancer. So we're learning more about how obesity affects cancer morbidity, it's a little bit more difficult to study then this link between obesity and cancer incidents but what we're starting to see is that indeed obesity is associated with adverse outcomes with respect to cancer mortality for a number of different cancers.
27:28 Colacino: So, in public health we try to think about intervening on obesity at multiple levels really. So there's the individual levels where we can always make recommendations to individuals, usually through their primary care physician to improve their diet, eat better, exercise more, lose weight so that's the personal responsibility angle. Of course we also know that there's a lot of systemic issues and social issues that promote obesity in different populations so it's really important to make sure that everyone has access to good grocery stores, make sure that everybody has access to parks and sidewalks so that they can move around more and get exercise easily. So we think that there's the individual factors all the way up to the social factors are where we could intervene on a public health level to try to influence this link between obesity and cancer.
28:13 Colacino: There's some potential interesting intersections between exposure to environmental chemicals and obesity and cancer that I think we're just starting to uncover. There are specific types of chemicals that we call obesogens that exposure to these chemicals seems to promote obesity. And so we've identified some of these in animal studies, we've identified some of these in human population studies but we're still at the very beginning stages of trying to understand whether exposure to these chemicals might influence cancer risk through this obesity pathway.
28:47 Colacino: So my lab's always been interested in really understanding how environmental factors influence cancer risk and cancer progression. I'm fortunate that I have great collaborators here that are really excited about obesity and the mechanisms that obesity cause cancer. And so one of my graduate students Evan Hill has been working on multiple projects in this area and his interest has really, I think rubbed off on me. It's really been because of my great collaborators and my great students that I also have got excited about this field as well.
29:24 S2: Thank you for listening to this episode of Population Healthy from the University of Michigan School of Public Health. We're glad you decided to join us and hope you learned something that will help you improve your own health or make the world a healthier place. If you enjoyed the show, please subscribe or follow this podcast on iTunes, Apple Podcast, Google Play, Stitcher, Spotify or wherever you listen to podcasts. Be sure to follow us @umichsph on Twitter, Instagram and Facebook so you can share your perspectives on the issues we discuss, learn more from Michigan public health experts and share episodes of the podcast with your friends on social media. You can also check out the show notes at our website, population-healthy.com for more resources on the topics discussed in this episode. We hope you join us for next week's episode where we'll dig further into public health topics that affect all of us at a population level.
- The Global Cancer Burden: Avoidable Causes from Lifestyle to Environment
- HPV Exposure and the Increasing Prevalence of Head and Neck Cancer
- Using Technology and Collaboration to Combat Cancer
- How Skeptical Epidemiologists Figured Out That Cholesterol Drugs Can Help Prevent Prostate Cancer
- Lung Cancer Will Remain Major Health Issue, Despite Falling Rates
In This Episode
Anant M. Kshirsagar Collegiate Research Professor of Biostatistics
Director of Biostatistics, Center for Healthcare Outcomes & Policy
Mousumi Banerjee is Research Professor in the Department of Biostatistics and Director of Biostatistics at the Center for Healthcare Outcomes and Policy (CHOP). She is also a member of the University of Michigan Comprehensive Cancer Center. Her methodological research focuses on tree-structured regression and ensemble methods, multilevel models, longitudinal analyses, survival analyses, and competing risks; with applications to cancer epidemiology and health services research. Learn more.
Associate Professor in Environmental Health Sciences
Associate Director, Office of Global Public Health
Associate Professor, Nutritional Sciences
Dr. Rozek uses population-level statistical and molecular approaches to address the environmental and epidemiological risk factors for cancer with an emphasis on US minority and global populations. With colleagues at academic institutions in Thailand, she has established bidirectional collaborative projects that address the temporal changes in cancer incidence for the purpose of informing cancer prevention and health policy decisions in the country. She has also developed community-based studies of unique cancer risk factors and predictors of cancer survival in northeast and southern Thailand. Learn more.
John G. Searle Assistant Professor of Environmental Health Sciences
Assistant Professor, Environmental Health Sciences
Assistant Professor, Nutritional Sciences
Dr. Justin Colacino is an Assistant Professor of Environmental Health Sciences in the School of Public Health. His research focuses on understanding environmental and dietary factors in carcinogenesis and cancer prevention. Specifically, the goal of his research is to characterize the environmental susceptibility of normal human stem cell populations, elucidating the etiology of sporadic cancers. Learn more.
Associate Professor, Epidemiology
Associate Professor of Global Public Health
Co-Leader, Cancer Epidemiology and Prevention Program, UM Rogel Cancer Center
Dr. Meza is associate professor in the Department of Epidemiology at the University of Michigan. Dr. Meza's research interests lie at the interface of epidemiology, biostatistics and biomathematics. In particular, he is interested in cancer risk assessment and the analysis of cancer epidemiology data using mechanistic models of carcinogenesis. Learn more.