Webinar: Working Smarter to Prevent Bladder Cancer: Understanding How Jobs and the Environment Affect Risk

February 13, 2026

Description: Dr. Sunil Patel and Dr. Stella Koutros discuss how work and environmental exposures can influence bladder cancer risk. They address the experiences of veterans, firefighters, and others who may face these hazards.

Year: 2026

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Full Transcript of Webinar: Working Smarter to Prevent Bladder Cancer: Understanding How Jobs and the Environment Affect Risk

Patricia Rios:          

Welcome, my name is Patricia Rios. I am the Director of Education Advocacy and your host for today’s webinar on Working Smarter to Prevent Bladder Cancer: Understanding how jobs and environment affect risk.

Bladder cancer is a complex disease with many risk factors such as age, gender, and genetics. Exposure to harmful chemicals can also put people at risk. For example, people who smoke are two to three times as likely than non-smokers to be diagnosed with bladder cancer, yet many bladder cancer patients have never smoked.

Scientists are learning that other kinds of toxic chemicals in our environment, meaning chemicals that we come in contact with where we live, work and play, are important contributing factors that can increase a person’s risk of developing bladder cancer. Based on growing body of evidence, more than a dozen chemicals and other industrial agents have been linked to bladder cancer alone. And to shed light on the connection between bladder cancer and toxins in the workplace and our environment, we are joined by two phenomenal speakers, Dr. Stella Koutros from the National Cancer Institute and Dr. Sunil Patel from John Hopkins Medicine.

I’m going to introduce our speakers and then hand over the screen to them for the presentation. So Dr. Koutros is a cancer epidemiologist in the occupational and environmental epidemiology branch in the Division of Cancer Epidemiology and Genetics at NCI or the National Cancer Institute. She is an internationally recognized expert in the design and the conduct of epidemiological studies to evaluate workplace exposures as risk factors for cancer and to clarify the causes of bladder cancer.

Dr. Sunil Patel is an assistant professor of urology and oncology at the School of Medicine at John Hopkins. He serves as director of the urologic oncology fellowship. His clinical and research focus is obviously urologic oncology with areas of focus in bladder cancer, testes cancer and kidney cancer.

Dr. Patel joined the John Hopkins Medicine in June 2020 with interest in environmental factors contributing to oncogenesis or development of tumors in urological cancers, particularly bladder cancer.

That was a short description of their very extensive background, and so we are honored to have them both here today so we can learn a little bit more about the connection. And so with that, I am going to go off camera and hand the screen to our first presenter, which is Dr. Patel. After Dr. Patel’s presentation, you will hear from Dr. Koutros. So without further ado, Dr. Patel, the screen is all yours.

Dr. Sunil Patel:

The goal of this session is really for Dr. Koutros and myself to highlight some of the occupational and environmental factors that we’ve been targeting and discussing at our think tank over the last several years and going into some of the key studies and the study designs, as well as a little bit the data and the results on some key factors.

So we’re going to highlight some environmental risk factors for bladder cancer. We’re going to look a little bit on the data on disinfecting byproducts, arsenic and nitrates, and look at some of the evidence that is pretty strong that we have for carcinogenesis for these environmental risk factors and some emerging and kinda uncertain links. And then really talk about the gaps in future research needs. Next slide, please.

Dr. Sunil Patel:

So as Patricia highlighted, again, and this is just a very general slide, but smoking again is the leading cause with smokers being two to three times more likely to develop bladder cancer. Environmental exposures, so we do know that working in certain industries like in the rubber, textile, leather, and/or with dyes, whether that’s hair dyes or aniline dyes or in clothing does increase risk.

And again, that includes both work and environmental. Secondhand smoke often gets misrepresented, but that is still another risk factor as we know for a lot of malignancies, bladder cancer included. Hydration is a very interesting one, and Dr. Koutros has done a lot of work in this as well, and we’re going to highlight a study that challenges this not drinking enough water and the fluid intake, but historically it’s been thought that poor PO intake or fluid intake increases bladder cancer risk by concentrating carcinogens in the urine, which potentially can be, but there’s some more data that may contradict that.

And as we know, chronic bladder irritation can cause bladder cancer. Again, a little bit different type of bladder cancer. We usually see that in squamous cell carcinoma, so a little bit different than neurothelial carcinoma of the bladder. However, that is still in the umbrella of bladder cancer. Next slide, please.

Dr. Sunil Patel:

So again, so smoking roughly attributes to around 50% of the bladder cancers. I know we highlighted this at the last year’s think tank, but it’s really what about the other 50%? As Patricia highlighted eloquently, that there are a lot of our patients in modern era that really aren’t smoking cigarettes and they’re developing bladder cancer. If we look at the historical trends, I believe around the 1940s and ’50s, there’s around 50%, at least the US population that smoked cigarettes or said that they did. If you look at the recent data probably in the late 2000 teens and 2020 or so, that number dropped down significantly down to anywhere from the 10 to 15% range.

So there has been a significant drop in smoking, but we haven’t seen that in the bladder cancer incidence rates. And so that begs the question again, what are the other factors? And so we do know from occupational studies, and again, Dr. Koutros is going to highlight this that, there are other risk factors, and this is really how we utilize our knowledge and how we learned about carcinogenesis in these other two areas and how that can lay the platform and set the field for how to really study these environmental risk factors. Next slide, please.

Dr. Sunil Patel:

And so this was just a really nice study that really looked at a case control, looking at men and women and looked at just smoking and its attribution to bladder cancer. And if you look at two different cohorts, it’s pretty consistent that smoking attributes to roughly around 50% of bladder cancer, both men and women. And so that has been really well studied.

And these large case control studies, again, done by our expert epidemiologist, namely at the NCI and a lot of colleagues of Dr. Koutros, as well as a lot of studies she’s done, has really led to our knowledge of population-wide studies on how these case controls can show what are the risk factors. Next slide, please.

That just tells you how many thousand patients were in each kind of cohort. So a very large case control study. Next slide.

Dr. Sunil Patel:

So let’s shift over to arsenic. So arsenic is naturally occurring metalloid, however, it’s also highly toxic. It exists in inorganic as well as in an organic form.

And arsenic has been one of those ones that have been studied for some time, and there is a strong association with bladder cancer. And over the next few minutes, we’re going to highlight a little bit about the studies in arsenic and what we know about arsenic and potential mechanisms. Next slide.

Dr. Sunil Patel:

And so arsenic exposure is a little bit variable. So right now, what we really think about exposure, we’re really attributing it to private wells. And so in the US, unregulated private wells are a major concern. For instance, in the Northern New England, bladder cancer rates are much higher. We’re going to highlight a key study, again, done by the NCI that showed this, but it’s much higher than the national average, and it’s largely attributed to arsenic in well water.

Historical pesticides, which were really done about probably 60, 70 years ago, were probably the biggest culprit. However, they’re not really used in modern era, but they still have a lot of leaching into the ground, hence into our wells as well. And then dietary exposures. So certain foods, particularly rice, can absorb arsenic from the soil, especially the water as well. And a lot of that has been done, and we see that in a lot of our Asian cohorts, and that’s been well studied, at least in Southeast Asia, as well as other areas of Asia. Next slide.

Dr. Sunil Patel:

Again, so arsenic has a pretty strong evidence that… Well, there is a strong evidence that inorganic arsenic increases bladder risk. Studies show that there is an increased risk with arsenic concentration in water as well. And we’re going to highlight a little bit about time and dose-dependent variables. And the IARC classifies arsenic in drinking water as a known carcinogen.

And again, a lot of this work was done and a lot of these statements have really come out from the key study done in 2016 by the NIH NCI linking bladder cancer rates and elevated bladder cancer incidents to the arsenic found in these private wells. Again, the New England study as we all, kind of New England water study, as we all call it. Next slide.

Dr. Sunil Patel:

And so this is a really nice figure that really highlights the incidence of bladder cancer and the mortality rates. And so when we’re looking at this slide, this really looks at two key time points. We’re looking at Caucasian men and women, and looks like, again, two time points, ’50 to ’79, 1950 to ’79, as well as the relative modern era, so the ’80s to 2000s. And again, the striking thing you can see is that bladder cancer mortality rates are clearly higher and concentrated, you see in the northeast, much higher than you see all over the rest of the US.

Also, Alaska’s in there as well, but this really was a big launch pad for that big pivotal study. Next slide.

Dr. Sunil Patel:

And so this slide, or excuse me, this study was led by Deborah Silverman over one of Dr. Koutros’s colleagues, and they looked at the very comprehensive study. And Dr. Koutros did talk about this study in detail at our think tank, but long story short is that this study was really well done and it really looked at two key things. One is that really showing that the arsenic exposure in private wells in New England varied. However, the higher amount there were higher incidents of bladder cancer.

They did talk, and they really looked at also different differences in the well types, in the shallow and deep. And we essentially found out that arsenic concentration was correlated to bladder cancer incidents. Additionally, again, when I earlier mentioned that the concentration or the volume of water potentially altered incidents, and this study did show that there was a little bit of a increased incidence.

So the higher volume or tap water that was drunk by these patient or volume of water, excuse me, not tap water, increased the incidence of bladder cancer, so challenges that dogma. Additionally, we found that there’s roughly a latency period around 40 years-ish from the exposure and this chronic exposure to the development of bladder cancer.

So unfortunately, it’s not one of those ones that if you drink well water once in your life, you’re probably going to get bladder cancer. This is usually repetitive over a period of numerous years in order to develop bladder cancer.

And interestingly, Dr. Koutros actually did a follow-up study similar to this, but you can see that the arsenic exposure in carcinogenesis was almost augmented in smokers. So arsenic has never been thought to be a mutagen by itself, but almost in synergy with smokers thought to be a kind of co-mutagen.

And Dr. Koutros in one of our studies found that that did increase the risk of bladder cancer. So arsenic exposure in combination with smoking did increase incidence. Next slide.

Dr. Sunil Patel:

And again, so talking about dosing. So when we talk about exposures and risk factors, we always think about, what is the time needed in order for you to be exposed under X chemical or toxicant, and also at what dose? And I think that comes into play. And so what we found in this study, that bladder cancer increases at higher levels of arsenic.

And this study found at a little bit higher levels than what the NCI found. However, that low to moderate still is uncertain, but there’s still studies that do show that it does increase the risk when you combine it with smoking, which Dr. Koutros found, and other genetic factors. And again, the genetic factors, it’s still an ever-changing kind of landscape right now, and that’s what we’re trying to learn a little bit more about. And again, sets the platform for how to really study these.

Dr. Sunil Patel:       

And so when we talk about arsenic and we talk about the strong association, we still do not have a really good example or good finalized mechanism of how this is carcinogenic. It’s been hypothesized that there are genotoxic effects and DNA damage, it can alter enzymes and create oxidative stress, which would promote carcinogenesis or interact with certain or repair pathways. I was talking to one of my colleagues recently and we’re in developing another study in environmental carcinogenesis, and we talk about almost the thought of evolution and how we’ve became from single cell organisms to what we are right now and how we’ve developed and all living things have developed mechanisms to protect themselves from the environment or the exposures they are exposed to.

And the human body has a lot of pathways and mechanisms to correct them, namely, a lot of our liver enzymes are actually meant to help combat a lot of these toxins.

And so we hypothesize that they’re potentially not just arsenic, but other exposures and other environmental toxicants could just have… Our bodies have not developed the protected mechanism. So we don’t really know for sure which way arsenic can, and it’s been hypothesized it can interact with a Sonic Hedgehog gene and create mutations there at the basal level, and that’s what creates carcinogenesis and bladder cancer. There was a study done in China about three years ago that showed it with a small study or a small sample size, but that was done all ex vivo.

But again, there’s multiple pathways and there’s a lot of hypothesis, and I think that’s going to be the next step of how, if we can figure out a mechanism of this carcinogenesis or potentially this co-mutagen, then we can figure out a way to target it or combat it. Next slide.

Dr. Sunil Patel:

And now shifting over to disinfecting byproducts, again, another environmental risk factor that’s becoming more and more evident and/or being studied more. And so DBPs, it’s a little tongue twister, 401 chlorine is used for disinfecting drinking water and when they react with organic matter. The most common ones are trihalomethanes, so THMs, haloacetic acids, and nitrosamines. And so those are the three most common ones. We’re going to focus a little bit on the trihalomethanes because those have been studied the most. Next slide.

Dr. Sunil Patel:

So again, what DBPs are the most concerning? Trihalomethanes are the most studied, so chloroform, bromaform, et cetera. Again, a lot of key component of disinfecting byproducts. There are also some suggestions that nitrosamines and other nitrogenous compounds may be known bladder cancer carcinogens, but we still don’t have a good grasp of all of the DBPs out there. Next slide.

Dr. Sunil Patel:

So from the epidemiologic literature, we do know that long-term exposure to these trihalomethanes is associated with increased bladder risk. Again, the risk is obviously, again, time-dependent, dose-dependent variables. There is an increased risk observed, especially household exposure levels, which is above 49 micrograms per liter.

There’s been some conflicting data, but there has been some good data showing that some studies do indicate that there’s a possible effect with showering and bathing, but I think the studies have been really conclusive in modern era and I think recently done at the NCI, showing that pool exposures really do not increase the risk. So it’s thought to be due to the ingestion, but they’re all potentially mechanisms of how we can be exposed to these. Next slide.

Dr. Sunil Patel:

And again, Dr. Freeman, another excellent researcher over at the NIH, NCI, really focuses on this and really found that it’s, again, what’s formed from chlorine and other disinfectants that clearly showed that there’s been elevated levels in these. And again, this was another two case control study. So it’s a very large study done by big case controls with thousands of patients.

And again, this study really highlights, and a lot of the other ones we just talked about really highlights how from the epidemiologic literature we find these associations and potential causal links to cancer development. And so Dr. Freeman did a beautiful job of this study, and I urge all of you guys to take a look at this study because it really highlights a good way to do these big large population studies. Next step or next slide, excuse me.

Dr. Sunil Patel:

And so in that study, Dr. Freeman found that bladder cancer was positively associated with total THM or trihalomethane ingestion via drinking water in the top 5% of the distribution study. There were positive associations with higher than 46 micrograms, so the top 5% compared to the lowest quartile, which is less than six.

And again, that study that she did did not support the association between swimming pool use and bladder cancer development. Next slide.

Dr. Sunil Patel:

And again, the mechanism of action, again, is all hypothetical at this point, but brominated THMs are metabolized and the reactive intermediates bind to DNA and they favor bladder epithelial cells, and they can lead to mutagenesis, again, causing DNA damage and then triggering a sequence and how a lot of cancers develop this repetitive sequence without being checked on and causing cancer’s growth. Oxidative stress, again, potentially… TSMs can create reactive oxygen species.

Again, another way that we think of sometimes even patients in obesity and cancer development, especially in kidney cancer, causing an imbalance of cellular proteins. And it’s hypothesized it can affect the NFKB pathway, again, which is heavily involved in regulation of cancer development. And then we look at the epigenetic alterations as well, causing DNA methylation. And then another aspect of cancer development, which I think we’re learning more and more about is endocrine disruption.

And as we know, endocrine and hormonal functions is very important and potentially can be protective as well. And THCMs may alter normal cell cycle and endocrine function, which can potentially create bladder cancer as well. Next slide.

Dr. Sunil Patel:

And then shifting into nitrates. So nitrates is another environmental risk factor that we’ve been looking into as well, we, meaning the whole bladder cancer community. And studies show that there is a positive association between higher nitrate concentrations in drinking water and an increased bladder risk, again, potentially amongst patients and people exposed to long-term. Again, so I think the key hallmark, there is some sort of longevity, with this like Dr. Silverman’s really show that there’s around a latency about 40 years.

So we potentially are thinking about the same thing for these other risk factors. Dietary sources, I think that that is one that, it’s another way that we can ingest and get nitrates. However, that’s not been truly a hundred percent proven, but high intake of nitrates and nitrates, essentially processed meats have been linked to increased risk, but we don’t really know the mechanism.

Again, and then the mechanism that we think can lead to it is just the endogenous formation of NOCs, which are probable carcinogens. And then another risk factor for nitrate in development is lower intake of antioxidants, vitamin C, E, which can inhibit the formation of some of these. Next slide.

Dr. Sunil Patel:

So this was a study done looking at the nitrate from drinking water in diets and bladder cancer amongst post-menopausal women, specifically in the state of Iowa. And they looked at around 250 bladder cancer cases, including 130 among women, and they looked at their public water supplies for greater than 10 years. And they found that there was a significant association with the exposure, so greater than four years of that drinking water with greater than five milligrams per liter compared to women who had zero years of that comparable exposure.

Again, another really good way to study this is the long-term or longitudinal studies of looking at patients and following them for several years and understanding their water supplies. And I think that’s a brilliant way that our epidemiologists really learned about these, is that understanding, getting these really good data from public water municipalities and getting good data for that.

So the study really did show that there is an association with dose, but also time. Next slide.

Dr. Sunil Patel:

And this, again, is another key study, again, done by Dr. Ward. And again, looking at ingested nitrates and nitrides in bladder cancer, again, and this is mainly through water supplies. And we believe that this is primarily from agricultural sources. So nitrogen and nitrates can be used and are commonly found in fertilizers and manure and human waste.

So we do know that they’re often used in our agricultural communities. So in Dr. Ward’s study, they found that the average drinking water nitrate concentration was above the 95th percentile compared to the lower ones in patients who developed bladder cancer.

So again, another kind of concentration variable seen and seen that there is an increased association with that as well. Next slide.

Dr. Sunil Patel:

Again, so if we really look at comparing the three that we highlighted today, we have arsenic, DBPs and nitrates. So arsenic, I would say we probably have the strongest evidence in terms of it being a carcinogen. Again, I think the mechanism is yet to be fully described. That’s something that we’re actually actively working on, Dr. Koutros and I. And really this was actually, commend BCAN for allowing this in patients from BCAN as well as all the researchers to create this almost a task force out of the think tank to really study this. And that’s one of our research goals is to figure out a mechanism for this.

DBPs, again, I think there’s moderate strength. I think there are good associations with bladder cancer, but we don’t have a true understanding of a lot of them. Again, I think the trihalomethanes have been studied the best.

And then nitrates as well, it’s still emerging. I guess there’s some uncertainty, I think there is clear an association. We’re trying to help understand that a little bit more as well. Next slide.

Dr. Sunil Patel:

And so the knowledge gaps in this are, I think I alluded to this several times, is precise mechanisms. I think finding the mechanism of how these are either mutagens or co-mutagens or how they disrupt our normal body’s checkpoints is going to be key in order to understanding bladder cancer development.

I think we made a lot of progress, and again, namely due to our brilliant epidemiologists at the NCI who really figured out and found dose associations, but I do believe that we can do better in this. And when is that ultimate trigger? We’ve hypothesized creating almost this calculation of a dose plus the time, and maybe that’s the number that we need to figure out, and that’s going to trigger someone to be an increased risk in maybe potential introduce screening.

And again, going to that time, the time needed. I think we’re learning that more.

And I think, again, Dr. Soleman’s study with the New England water study was really pivotal in that, but I think for a lot of these other environmental risk factors, even a lot that we did not cover today, that’s something that’s absolutely key. These three things, the mechanism, the dose and the time. Next slide.

Dr. Sunil Patel:

So future directions, like I said, mechanistic studies I think are going to be key. And another thing is really understanding the exposome. So the exposome is, again, everything that we are exposed to, and we’re having more developments in actually studying the exposome. So it’s really hard to study exposures.

And a lot of this are retrospective studies where we’re going back or we’re doing longitudinal studies and we’re following patients for X amount of years, but we’re maybe getting epidemiologic studies or information from that saying their water quality, their duration of exposure, potentially the dose of what they’re exposed to. But sometimes that’s a very generalizable thing. Sometimes we don’t know the individual.

Also, we have not been able to really correlate that to in terms of that individual’s cancer. So what we’ve been trying to do here at Hopkins, and actually Dr. Koutros and I are doing a study together, which is currently in progress, is identifying a small cohort of patients in studying their hair, blood, and urine, which can potentially hold a little bit of more of what they’ve been exposed to, comparing that to what their environmental exposures that were known through public data and epidemiologies and looking directly at their tumor.

And that kind of gets to the last bullet point for this is really study the interplay of the genetics of the individual, whether that’s mainly their germline. And there’s been a lot of germline hole-wide association studies that have been coming out and tumoral genetics, so the somatic aspects of these tumors, and again, their environment and their exposome, and really creating a way to look at this from three different ways. And I think that would be the ultimate goal in environmental carcinogenesis. If we can really study this wholly, that would lead us to more advancements in bladder cancer.

 Dr. Stella Koutros:

So today, as the others said, I’m going to be talking about occupational exposures in bladder cancer. Like Dr. Patel, I should say, and I think we always say that the number one risk factor and the number one way you can prevent bladder cancer is to quit smoking. Smoking is really the most important risk factor for bladder cancer, but we’ve also recognized that occupational exposures are really important as well and can account for up to a quarter of bladder cancer cases. So I’ll be focusing in on those in my next few slides.

Dr. Stella Koutros:

I’ll talk a little bit quickly and briefly about some of the terms we use when we think about occupational studies and the different types of studies. And then I’ll dive into what key things we know already about occupational risk factors in bladder cancer, and then just a few words at the end about prevention.

Dr. Stella Koutros:

So, one of the primary considerations when reading an occupational study or a study about an exposure is the assessment of that exposure. So we call that exposure assessment, and that is really just a fancy word for how you obtain accurate and precise estimates in the most efficient and cost-effective way. So if a study’s trying to look at a relationship between an exposure in bladder cancer, we really want to understand what they’re doing to kind of characterize that for a person and how they characterize it over that person’s life.

Dr. Stella Koutros:

This has really important implications for the quality of the study. So today I’ll talk about some of the exposures that have some of the most evidence for bladder cancer, but also if there’s one thing I can leave you with is thinking about if you end up reading a study on your own, what you might consider about the exposure assessment will really help you understand what is really key about understanding the quality of that study.

So sometimes in occupational studies, we study sort of occupational groups like truck drivers, and that’s what we sort of call occupation or industry only. We sort of look at just a group of people who are working in a certain type of job. It’s even better if we have some more information, like how long a person did that, like how many years they did that, but it’s even better when we have really more detailed information about specific exposures.

Like if you’re a truck driver, were you exposed to engine exhaust, and if you were exposed to engine exhaust, even better if we can sort of quantify that in a more quantitative way. So the more we can do that, the sort of better the quality of the study tends to be and sort of the better the inferences we can make about the risks for bladder cancer.

Dr. Stella Koutros:

So, one source of compiled information about cancer comes from the International Agency for Research on Cancer. This table’s a lot, but it’s a little bit of a summary about many of the occupations and workplace exposures that have been classified as bladder carcinogens because there’s been decades of research in showing certain positive links and the things that are in the light blue are those with, which they have considered have sufficient evidence in humans. And the little PDF link at the bottom is a link to a table where you can look at sort of what’s known about bladder cancer. I’ve just put some of the occupational things here, but they include other things as well.

Dr. Stella Koutros:

One kind of key or commonality between a lot of the chemicals that were in that table are these group of chemicals that have a similar chemical structure. They’re called aromatic amines. And we know that these particular chemicals are specifically damaging to the bladder and have largely been identified in studies of workers who ended up developing very high rates of bladder cancer in sort of different occupational settings.

My group also has conducted some really large scale genetic studies where we’ve also shown that important sort of inherited genetic variation and certain key genes that are responsible for sort of metabolizing these chemicals and getting rid of them from the body are important modifiers of risk. And many of the people affected by these exposures are typically in industrial and manufacturing settings, which have become a little bit less common over the last several decades. So next, I’ll just talk about a few other exposures that are more commonly reported among contemporary occupations.

Dr. Stella Koutros:

So metal-working occupations have been associated with increased bladder cancer in over 20 studies. So some specific jobs that have these exposures are precision metal workers or metal-working or plastic-working machine operators. And people who do these jobs are using what are called metal-working fluids. So they’re used in metal machining to lubricate cool and remove debris from metal parts that are being drilled, ground or milled or some kind of type of machining work. So these metal-working fluids contain some certain chemicals that are suspected, some known and some suspected to be carcinogenic.

Dr. Stella Koutros:

Another sort of exposure that’s been linked to bladder cancer is exposure to diesel exhaust because of several studies of specific occupational groups who have high levels of exposure that have had increased bladder cancer risk, in particular truck drivers and bus drivers, but not a lot of studies really could go beyond that and get to those more quantitative estimates of exposure.

And initially, when IARC reviewed some of the literature, they said, “Well, we’re not really sure there’s not really enough good data about this for bladder cancer yet.”

Dr. Stella Koutros:

One thing that I have been involved in is a combination of two case control studies that were conducted around the same time period, and they were similar in size.

One was in Spain, and another one is here in New England, which is the study that Dr. Patel had mentioned. Both of these studies had identical questionnaires. We collected really detailed information about a person’s lifetime occupational history, as well as these job modules to get really detailed information on different exposures.

And we pulled the data from these two studies.

Dr. Stella Koutros:

And in 2020, we published results that found that workers had elevated levels of diesel exhaust exposure had a higher risk for bladder cancer compared to people who were not exposed.

And so this was, I think, a study where we were able to provide some of that quantitative exposure data, which was sort of an element that had been missing on this topic before.

Dr. Stella Koutros:

Another set of exposures of interest that we’ve been sort of studying lately are organic solvents. So many of the occupational groups that have been noted to have higher bladder cancer rates happen to also have exposure to solvents, including people in dry cleaning and rubber textile manufacturing, painting.

And there’s sort of a diverse sort of set of tasks and chemicals that would sort of include the use of solvents, including degreasing and cleaning. It’s also present in gasoline and a lot of paints and glues. So there are a lot of different sort of sources for potential exposure to solvents.

Dr. Stella Koutros:

So a few years ago, there was this really large study from the Nordic countries that showed that there was some suggestion of an association between certain organic solvents and bladder cancer risk. And two of the solvents in this group seemed to be associated with a risk at the highest levels of exposure.

And another one of these chemicals, one at the bottom there, trichlorethylene is something that’s used very similar to a chemical that’s used in, it’s a dry cleaning solvent, which has been also linked to bladder cancer before. So there was some initial sort of signal here there might be something going on for bladder cancer.

Dr. Stella Koutros:

And a little after this study, there was a large prospective case cohort study of Norwegian offshore petroleum workers, which showed an increasing exposure to benzene after adjusting for smoking and other factors and an increased risk of bladder cancer, sort of building on this literature for linking solvents in bladder cancer.

Dr. Stella Koutros:

So to follow up on these findings, my colleagues and I at the NCI looked at the relationship between solvents and in the general population of people who developed bladder cancer in the New England region where our study was conducted.

Dr. Stella Koutros:

And we were able to use these lifetime job histories and specific details again about the tasks and chemicals that people used on the job and found that there was also, we did find these increasing risks with exposure to sort of benzene, toluene and xylene. And then the three is a group, which is called BTX because they kind of often co-occur. And an important additional element of this is that we’ve also been able to really carefully adjust for smoking and also other types of occupational exposures because there are many that have been linked to bladder cancer as well.

Dr. Stella Koutros:

This chart just shows some of the jobs that were reported to have the highest levels of exposure to BTX. And you can sort of see here, they’re color coded. Several types of machine operators in different industries can be exposed in shoes and textiles, but also auto mechanics and workers involved in autobody repair.

This group was particularly interesting because they ended up reporting a lot of gasoline use as a solvent. It turns out it’s fairly common for people to use gasoline as sort of a cheap solvent for degreasing and cleaning parts.

Dr. Stella Koutros:

And shortly after our study, IARC summarized sort of the overall cancer literature on gasoline and found that there was enough sufficient evidence in the literature in human studies that exposure to gasoline was shown to increased the risk for bladder cancer. And this is the summary of those findings which are online.

And it includes several… This would impact and sort of cover several working populations, including service station attendance, mechanics and workers in sort of production and transportation of gasoline. So potentially a lot of occupational groups exposed.

Dr. Stella Koutros:

So as I mentioned earlier, there’s evidence that some occupational groups have these higher rates of bladder cancer and recently evidence had also been synthesized about firefighters and the increased risk for bladder cancer observed in this population.

And sometimes we can observe these higher rates in working populations, but we sort of have to do more work to understand what are the underlying specific exposures causing these elevations and risk. And so firefighters are exposed to a really wide range of things, including combustion products, diesel exhaust, asbestos, other building materials, and several other really heterogeneous exposures.

Dr. Stella Koutros:

Another group of interest are those who serve in the military. Like firefighters, this group is exposed to a really wide range of suspected carcinogens depending on the timing and location of military service and occupation. So there’s still a lot more work needing to sort of help us understand what the direct connections are between exposures and military service and potential risks for bladder cancer.

Dr. Stella Koutros:

Ultimately, the studies we sort of really quickly covered today are important for identifying sort of occupational carcinogens in the workplace so that we can take some action to minimize these exposures and decrease any exposures when we can. For example, over time, diesel technology has changed really significantly to drastically reduce emissions compared to engines decades ago.

And our education about the risks from workplace exposures and how we can protect ourselves is also really an important strategy for reducing the burden of these exposures. In the future, we may even be able to develop some strategies for screening high risk populations for early detection as those kind of methods improve in the clinic and to try to prevent the development of bladder cancer altogether.

Patricia Rios:

So with that, I want to transition to some of the questions that we have received from our listeners. Dr. Koutros, there’s many questions focused around the smoking. And sorry, I was just reading the chat. I got a little distracted. So I think this goes back to the dosage and timing conversation that Dr. Patel was discussing, but the effects of smoking history, I guess many of our listeners want to know where does the risk increase?

Does it have to be continuous? What if it was only a pack for 10 years? So I guess the dosage and the timing is sort of, if you have more insight to share around that.

Dr. Stella Koutros:

Yeah. So we know pretty confidently that if you ever smoked, you have higher rate of bladder cancer. And yes, the number of years and the packs per day you smoked all definitely influence that. So people who are current smokers at the time of diagnosis, regardless of how many years, they tend to have longer duration of smoking, but they have the highest risk of smoking. They have about a four to five time higher risk compared to never-smokers. People who are former smokers have a lower risk, about two to three times higher than never-smokers. And it does increase with duration, but regardless of whether you smoked for 10 years and then maybe stopped for 30 or 50 years, that 10 years of smoking is still enough to increase your risk of bladder cancer compared to not smoking. So we do know that. And yeah, those things are important.

And part of the reason that with the exposures we talked about today, we want to get a sense for that history because we know that bladder cancer and a lot of cancers have a long latency. We know they develop many, many years down the road. So even those 10 years of smoking that you did or the few years you might’ve worked in aromatic amines manufacturing facility, those will still be important many decades later.

Patricia Rios:

Okay. Thank you for answering that. How about secondhand smoking?

Dr. Stella Koutros:

Yeah. So secondhand smoking has been a little bit of a mixed bag. I mean, the results in the human studies and the epidemiologic studies have been mixed. There are some studies that have shown positive associations, some studies have shown it’s really not that much. So I would say compared to tobacco smoking and even some other smoking, I think somebody said something about cigars, but cigar smoking has also been linked to bladder cancer risk. I would say it’s a little bit more mixed about secondhand smoking, what we really know for sure.

Patricia Rios:

Okay. Thank you. And so what would be an advice that you would give to those who are exposed to secondhand smoke, say people who work in casinos?

Dr. Stella Koutros:

Right. I mean, I think it’s difficult, right, because one thing I should have said, a lot of… I think I put in my slide that some exposures are modifiable, but when they’re in our workplace, it’s not exactly voluntary. We have to work and people have to make a living. And so it’s difficult to sort of balance that. And we kind of have to understand the risk for bladder cancer through that lens of these voluntary and involuntary exposures. But obviously we would recommend that exposure to cigarette smoke, we would like to limit as much as possible.

Patricia Rios:

Thank you. So you talked about different, so occupations, hairdressers, firefighters. And so military, for some of these, should there be some sort of surveillance program, particularly those that have been exposed and what that may look like in terms of screening urinary tests, for example?

Dr. Stella Koutros:

Yeah. So we don’t have right now a really sort of validated screening test for bladder cancer. So that makes it difficult to make any recommendation for screening programs per se. Certain other cancers have recommended screening tools that have proved to be useful and we haven’t gotten there with bladder cancer yet.

There’s a huge amount of clinical and research work focused on this question in particular, sort of trying to see whether we’ll be able to get to a place where we can look at a person’s urine and blood and see if we can detect cancer early. I think there’ll be a lot of development in this area over the next 10 years, but because we don’t have that yet, it’s difficult to recommend who should or shouldn’t be screened.

But I think we may eventually want to consider if we do end up having a test that might work that way, what high risk groups could be targeted.

We’ll see. All of that is kind of a TBD at this point.

Patricia Rios:

Got it. I think that’s something that we’re all looking forward to over the next 10 years, for a screening tool to become available. And so there’s a question about whether research has been done looking at the substances that healthcare workers are exposed to, particularly chemotherapy?

Dr. Stella Koutros:

I actually don’t know the answer to that question with respect to healthcare workers. Maybe Dr. Patel would’ve been better for this question with respect to actually people who have received maybe chemotherapy for other cancers. I’m not sure if that’s what the question is referring to. I could get back to you on that, but I’m not sure.

Patricia Rios:

I think it was more like healthcare workers, I think for example, x-rays, radiology, the exposure that comes with that.

Dr. Stella Koutros:

Oh, okay. Well, if it has to do with radiologic sort of risks, those have not been determined among healthcare workers for bladder cancer. What has been identified is that people who have been exposed to radiation, either pelvic radiation for some other cancer diagnoses, there’s evidence there that people who’ve had the type of exposure have increased risk of bladder cancer in the future.

Also, information from sort of radiologic events like Chernobyl, we see elevated rates of bladder cancer after those kind of big events. So there is a body of evidence in some specific settings that radiation is a risk factor for bladder cancer.

Patricia Rios:

Okay. And I just got a note from the person that asked the question, what about administering or mixing chemotherapy? Is there any data on that?

Dr. Stella Koutros:

No, I’m not sure. I don’t think there’s any data on that at this point, but I actually think it’s a really interesting question. And I believe that… I actually think some of our colleagues in Canada are thinking about something similar to that. But as of right now, I would say we don’t have enough information on that.

Patricia Rios:

Okay. Thank you. I think Dr. Patel talked about other factors that elevate the risk for the exposure. So there’s a question here from one of our listeners who wants to know, as a hairstylist who has a dad who just had bladder cancer, is my risk higher due to the genetic factor?

Dr. Stella Koutros:

Yeah. Well, just considering the fact that your father had bladder cancer, that is a risk factor. So people who have a first degree relative who have bladder cancer do tend to have a higher risk of bladder cancer themselves. So we do have enough information that there is a risk related to genetics in that regard. And what those genetic factors are exactly is still something we’re trying to understand more and more about. And we’ve done a lot of genetic studies. I had it at my top there, the link to one of our sort of larger comprehensive studies on genetics, and we’re understanding more about the genetic contribution, but having a family history is definitely a risk factor.

Patricia Rios:

Thanks for addressing that. And so we’re almost at time, so I have two more questions. The one question is, there’s a lot that I hear around microplastics and the risk. Is there any evidence, data on microplastics at the moment and any connection to bladder cancer?

Dr. Stella Koutros:

Sure. Right now there is no evidence about microplastic exposure and bladder cancer risk. One of the biggest reasons is what I said about exposure assessment. This is going to be a really challenging thing to study for cancer because it’s a relatively newer exposure and we understand it could take decades for something to sort of manifest, but also we haven’t set up studies up until this point to deal with the contamination issue from plastic.

If you think about it, the blood draws and the tubes we use, all of that is plastic. And so even for some of our studies where we have some banked biological sample collections, it will be really difficult to use that or leverage any of that data in the context of this contamination issue. And so people are just beginning to deal with some of those considerations and try to develop some studies to understand what the health effects might be, but it’s a very new area and right now we do not have any information about bladder cancer risks specifically.

Patricia Rios:

Okay. And what you mentioned was a great transition to my last question before we close, which I’m going to couple with another question. So the first piece of that question is, what can patients do to help advance the knowledge in the field of these exposures, risk factors? And then also, what can patients and their families do to reduce their risk?

Dr. Stella Koutros:

Yeah, I mean, I think part of the reason that Dr. Patel and I are always really happy to be here with BCAN in the community is because I think communicating these risks and educating people is one of the number one ways you can pass along that information to your family.

I had a researcher who was here and I was talking about gasoline. He was like, “Oh my God, I like to work on repairing, putting old cars together. And I use gasoline all the time all over my hands just because to do this stuff.” And I said, “Well, you might want to consider wearing gloves when you do that.” Or in the context of environment for people who might be on a private well, communicating with you or other relatives to make sure you test your wells, to make sure that the levels of arsenic are not above what we want them to be because they’re not regulated the same way public water supplies are regulated in the United States.

So hearing what the key risk factors that we already know about and trying to pass that information along to your family, even if you’re a bladder cancer patient already, passing that knowledge on to others is, I think an important thing that we’re doing here and that I always appreciate BCAN’s invitation to share that information.

Patricia Rios:

Yes. Knowledge is power. Thank you, Dr. Koutros for being here with us today and for sharing this information and shedding light on all these different occupational, environmental risk factors that we’re exposed to on a day-to-day.