Investigating cancer clusters 

National Public Radio (NPR) Talk of the Nation/Science 27jul01

ANCHORS: IRA FLATOW

Now turning from criminal investigations to scientific investigation. You may have seen books or movies about environmental defenders tracking down companies that have polluted their communities, causing health problems, you know, movies like "Erin Brockovich," and "A Civil Action." But few investigations of environmental health and safety go the way they do in movies, like everything else in life. Around the country, citizens groups complain of cancer clusters in areas where there seem to be more cases of disease than should rightfully exist. But it's sometimes hard to say that if there is even a problem there or just maybe it's a statistical fluke. And investigators must hunt down and follow up hundreds of different factors as they try to explain the causes of such clusters.

And this week, residents of Fallon, Nevada, are in the plans of the Centers for Disease Control for assisting the state Health Department with an investigation into cases of childhood leukemia around the town. And members of other communities around the nation have called for investigations into disease clusters in their neighborhoods. For example, there's a very famous case still ongoing, costing millions of dollars to investigate an unusually high occurrence of breast cancer on Long Island. So we're going to be talking about the challenges of investigating cancer clusters in communities for the rest of the hour. So if you'd like to talk to that, if that's something that's on your mind, give us a call. Our number is 1 (800) 989-8255; 1 (800) 989-TALK. And if you want more information about what we're talking about this hour, please, you're invited to surf over to our Web site at sciencefriday.com.

Let me introduce my guests. Mary Guinan is the Nevada state health officer. Her office is looking into the town of Fallon and she joins us today from her office in Carson City, Nevada. Welcome to the program.

Dr. MARY GUINAN (Nevada State Health Officer): Thank you very much.

FLATOW: You're welcome.

David Ozonoff is professor and chair of the Department of Environmental Health at the Boston University School of Public Health in Boston. He joins us by phone from there.

Welcome to the program.

Dr. DAVID OZONOFF (Department of Environmental Health, Boston University School of Public Health): My pleasure.

FLATOW: You're welcome.

Raymond Neutra is the chief of the Division of Environmental & Occupational Disease Control at the California Department of Health Services based in Oakland and he joins us by phone from his office there.

Welcome to the program.

Dr. RAYMOND NEUTRA (Chief, Division of Environmental & Occupational Disease Control, California Department of Health Services): Thank you.

FLATOW: Mary Guinan, do we know what's going on in Fallon, Nevada?

Dr. GUINAN: Well, all we know is that there's an increase in the expected number of cases of childhood leukemia and we're trying to investigate why.

FLATOW: Mm-hmm. And how long has this been going on for?

Dr. GUINAN: Well, we first recognized the epidemic or cluster in July of 2000. So it's just a year.

FLATOW: Mm-hmm. David Ozonoff, the people around Fallon have been quite concerned about the health of their town. Don't they have a right to be?

Dr. OZONOFF: Oh, absolutely. They have a right to be and the first question that always occurs to either an individual or a community when they have a problem like this is, 'Why me or why my community? Why my family? Why did this happen to us?' And they're seeking an explanation and essentially what we have here is a community in pain. And it needs to be looked after by the people who look after the welfare of communities from the health point of view, which are public health people.

FLATOW: Mm-hmm. Raymond Neutra, there have been many cases, many famous cases of disease clusters. There were seven cases of brain cancer in Los Alamos in 1990. I mentioned the elevated cases of breast cancer in Long Island just to name a couple. How many claims of clusters do you think occur each year around the country? Are they in the hundreds, people getting in the hundreds of claims of clusters?

Dr. NEUTRA: It could be. And if people look systematically, they would see lots of clusters, just on the basis of statistical variations. There's a lot out there that is statistical variation and yet Dr. Ozonoff is right that when one of these clusters is noticed and people ask the question that any reasonable person would, why is this here, is there something that could be changed to make it go away? And is that thing still operating or was there something operating in the past that might have created a problem?

FLATOW: All right. We're going to take a short break, as we usually do this time on the program, and we'll come back and talk lots more with David Ozonoff, Raymond Neutra and Mary Guinan--talking about disease clusters. So don't go away. We'll take your questions. Get them ready, we'll be right back after this short break.

I'm Ira Flatow and this is TALK OF THE NATION/SCIENCE FRIDAY from NPR News.

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FLATOW: Welcome back to TALK OF THE NATION/SCIENCE FRIDAY. I'm Ira Flatow.

We're talking this hour about how to investigate cancer clusters with my guests, Raymond Neutra of the California Department of Health Services in Oakland, Mary Guinan of the Nevada state health--she's the Nevada state health officer and David Ozonoff, who is professor and chair of the Department of Environmental Health at Boston University School of Public Health in Boston.

Our number: 1 (800) 989-8255. So, Mary Guinan, what is the plan? How do you develop a plan to investigate these clusters?

Dr. GUINAN: Well, I went to the experts, asked for assistance on how to do this, knowing full well that investigation of cancer clusters rarely turn up anything, despite "Erin Brockovich" and "A Civil Action." And got some help from a number of different federal agencies and experts, including Dr. Neutra, by the way, whom I called and knew he had a great deal of experience in this. And then we decided what we had to do, the first thing we had to do was to be sure that there wasn't something in the community that was an immediate hazard. And that was our first attempt. We interviewed the families of the children for exposures to any number of things and found out all of the information that we could from the time of conception of the child to the date of diagnosis on exposure of the parents and the child. And then to look at all the possible environmental things that are happening in the community. As you know, when there is a cancer cluster, most people feel that the environment is the cause of it. And our job is to go and find evidence for or against all of the possible things that may be contaminating the environment where this cluster exists. And that's what we did first.

And at the end of that, see, what was unique about this particular cluster is we identified it early. Usually, investigation of clusters occur when the cluster is over. And we identified this in July of 2000. There were four or five cases at that time. To date, we now have 14. So that we don't know if it's over. So we started the investigation early and we kept having cases. So, of course, we don't know when we're finished this preliminary phase, but we've analyzed the preliminary data and can find no evidence of something right now, immediately in the environment, that is causing harm.

FLATOW: Mm-hmm. Dr. Neutra, that would match then, I guess, every--just almost every other case of a cluster that is attributed to something in the environment. From what I read, no one has ever been able to link an environmental case--there may be occupational cases and things like that, but not something that's purely in a residential environment to a cluster.

Dr. NEUTRA: I don't think that's true. There are several documented cases in the literature where asbestos or asbestos-like agents were present in a residential setting. There's a famous case from the center of Turkey, in Anatolio, where there was--where one would have expected a fraction of a case of mesothelioma. There are close to, I think, 100 cases in this little village over a 10-year period; something like 20,000 times more mesothelioma than you would have expected by chance. And it turned out that those folks lived in caves and in rock dwellings made out of rock that was containing an asbestos-like agent and they were getting an industrial kind of exposure in their everyday life that--in their residence.

And there are some other cases of towns that are near asbestos mills and there was a recent case from some place in Micronesia where there was an asbestos-like material in the whitewash that they were putting on buildings and it was in that area. Not so much a neighborhood cluster, but that whole island of people that used that whitewash had greater mesothelioma, a cancer of the lining of the lungs and the abdominal cavity.

But it's interesting what characterizes those rare cases where epidemiologists have been able to find an explanation and that is, this is an agent that stays in the environment and it stays in the body so that even though there's a long incubation period to mesothelioma, decades, still one can find the responsible agent lurking around. One can look in the body and identify it there. Most environmental agents don't behave like that and that's why our--one of several reasons why our batting average with cancer clusters or other chronic disease clusters, with long incubation periods, is so much worse than our batting average with clusters of infectious disease where we do really well on that and it's a staple of public health practice.

FLATOW: Mm-hmm. 1 (800) 989-8255 is our number. Let's go to the phone. Carrie in Fallon, Nevada. Hi, Carrie.

CARRIE (Caller): Hi. How are you?

FLATOW: Fine.

CARRIE: I have actually two questions. They kind of answered part of one of the questions that I have. Aren't we also looking at all the autoimmune diseases that are also in our community? I live in this community that you're talking about right now and, you know, I just have so many friends that have other autoimmune diseases as well and I'm just wondering if when the epidemiologists look at that, are they also examining the autoimmune diseases in relation to how the cancers are? You know, that that may be one way that's being manifested in our community through these childhood leukemias. What about the other autoimmune diseases like the arthritis and the lupus that's in our town. There are just more people than you can count that have those diseases.

FLATOW: Is that right? Mary Guinan, is that right? Do you...

Dr. GUINAN: Well, Ira, this brings up a big problem that we have in tracking chronic diseases. There's no tracking system nationally or statewide to follow chronic disease. We do have a cancer registry so we do have documentation of cancer. We don't have either a national reference or a statewide reference for any other disease. I would like to mention that leukemia is not an autoimmune disease. It is not an autoimmune disease. It is a cancer of the immune system. An autoimmune disease would mean that there is some--the immune system is focusing its attention against itself, so that the immune system is attacking the cells of the body. That is not what happens in leukemia.

So that--but we haven't found an increase in cancer in adults or in other cancers, looking at the cancer registry. And this is one of the things that has been brought up in the US Senate where there has been a proposal to--and there's a bill working its way through Congress--to have the states follow chronic disease. And not only follow chronic diseases like we do reported infectious diseases, but also to have environmental toxins tracked. So then we could then take these databases and say, 'OK, is there an excess of mercury?' When there is a cluster, we can look at what the environmental agents are in that environment. But because we don't have that, we have no way of comparing whether there is an excess of other diseases in the community.

FLATOW: David Ozonoff, aren't you part of an effort to try to map the instance of diseases and match them with pollutants?

Dr. OZONOFF: Yeah, absolutely. Let me comment on a couple of things that have been said. First of all, I have the easiest job of the three of--my two colleagues here. Being in the state health departments they're really the people on the front lines, and they're the ones who have to deal with these emergencies, essentially, and that's what they are when they come up. As an academic, I have, you know, the luxury of being able to stand back a little bit and look at this with a slightly more detached point of view.

And the question about autoimmune diseases is a really interesting question. Those are diseases, first of all, that do involve the same kinds of cells as in the blood system, and there are agents that are implicated both in autoimmune diseases and in leukemia. Perhaps the most famous example is trichloroethylene, or TCE, which was the same chemical that was in the Woburn water supply, and that was the leukemia cluster that was part of the book "Civil Action." So when you see leukemias and autoimmune diseases in the same place, it does raise a red flag.

Now we don't know, as far as I can tell from the conversation here, that autoimmune diseases are increased in Fallon, Nevada, and the reason is that we don't really know how much to expect and we can't really count up all the autoimmune diseases without some kind of a registry system, which doesn't exist. But it does raise some very interesting questions and probably should be looked at very carefully.

Now the question that Dr. Neutra raised about many clusters appearing if you were just to look systematically--we are starting to look systematically by trying to develop methods to map cancer rates, looking for hot spots. A cluster can be thought of sort of as a hot spot of cancer risk in the geographic area and over a certain period of time. It's remarkably difficult to do that. It would seem like it would be an easy thing to do, 'cause one assumes that, you know, the data is routinely collected. But, in fact, you know, cancer can only appear where people live, and people don't live uniformly. They cluster in cities and towns and suburbs and all sorts of places.

And so you do see--if you just map the cancer cases, you'll see clusters all the time. Those clusters are essentially representing where people live, not necessarily where something bad is happening. So you have to have special kinds of methods in order to see those hot spots after sort of taking into account the uneven distribution of where people live, and not only where they live but the kinds of people who live there. So if a lot of old people are living in a particular area, maybe there's a nursing home in a neighborhood, you'll see lots more cancer and a higher mortality rate in that area just by virtue of the age of the population.

So that's one major problem, and that's one reason why what looks to be a cluster might not be a cluster. On the other hand, there might be lots of clusters that don't look like clusters because they get sort of covered up by the same kinds of factors. And so we're trying to develop methods to visualize those clusters without all those kinds of extra things getting in the way.

The second major problem that we have is that, when you do find a cluster, which are sort of usually neighborhood-size things, the techniques of epidemiology aren't really very much good for them. All three of us make our living doing epidemiology, so I'm not trying to badmouth how I make a living, but the truth is that epidemiology is a very insensitive way to find things. A definition of a public health catastrophe that I once made just in jest was that a public health catastrophe is a health effect that's so powerful that even an epidemiological study could detect it. And pretty much, that's true. You really have to have powerful things going on before the method that we are employing here can even see it.

FLATOW: Like Legionnaires' disease or HIV or something that just jumps out...

Dr. OZONOFF: Right, something that's...

FLATOW: ...through statistical numbers. Yeah.

Dr. OZONOFF: ...very rare and unusual and jumps out, because you never see it otherwise.

FLATOW: Yeah. And in--so there may be--these clusters may be actual and sometimes they may be hidden. I mean, they may be at...

Dr. OZONOFF: They may be hidden.

FLATOW: They're real clusters with real environmental problems, and they may stay hidden for that reason.

Dr. OZONOFF: Exactly.

FLATOW: Huh. So--but if we say the bulk of these clusters are statistical, and that's how we hear epidemiologists explain these things, how statistically does a cluster clump itself?

Dr. OZONOFF: Well, first of all, let me say that we don't have any idea whether most clusters are random in that sense or not. The way they could arise--if you imagine a map, if you threw darts at a map, some of the darts would be closer together just by chance than others, and that could be a cluster. But we don't have adequate methods to tell whether the clusters that we see are random or not. Most of the statistical methods that we use, in fact, are very insensitive to real clusters occurring. We know the real clusters are there because we can generate them with a computer, and then when we apply the statistical methods, the statistical methods say that they're random.

FLATOW: We're talking about clusters, disease clusters, and probably concentrating on cancer clusters this hour on TALK OF THE NATION/SCIENCE FRIDAY from NPR News. I was reading an article in New Yorker, recent article, in which they quote two pioneering psychologists, Daniel Kahneman and Amos Tversky in 1971, identifying a systematic error in human judgment which they called the belief in the law of small numbers. And it says, 'People assume that the pattern of large populations will be replicated in all its subsets, but clusters will occur simply through chance.' Can you explain that a little bit? David, do you know what they were talking about, the belief in the law of small numbers?

Dr. OZONOFF: Yes. One reason that epidemiological methods work very well for large populations is because all the little fluctuations get sort of evened out and smoothed out. But when you have very small populations, then unusual excursions are going to happen. So, for example, if I had a fair coin and I flipped it a thousand times, it would, you know, come up heads somewhere around 500 times, maybe a little bit more, a little bit less, but on average, it would be about .5. It may be .51 or .49 or .48. But if I flip a coin just twice, it could easily come up heads 100 percent of the time. And so that would look like a very unusual occurrence, but, of course, we know it isn't.

FLATOW: So it's like standing back from someone's face. If you look at the whole population of the US you won't see the little pimples there. If you get closer you may see a cluster of the pimples...

Dr. OZONOFF: Yes.

FLATOW: ...signifying something different has happened in those places. And are you saying, then--but the statistical techniques are not powerful enough to find these clusters?

Dr. OZONOFF: Exactly. They're--in fact, we know they've been tested out by a number of researchers. They're quite insensitive. And how do we know what a real cluster is? Well, the answer's, you know, fairly easy. You can simulate a cluster with a computer, have the computer put, you know, points on the map, but make sure that it clusters them, and then you can use those points and apply these statistical methods. And when that's been done, they find--or they tend to say much more often than not that these patterns, points on the map, are not clusters; they're there randomly. And that's just because we just don't have very powerful methods to find them.

FLATOW: Raymond Neutra, you agree?

Dr. NEUTRA: Not quite. I agree with what David just said, but not the inference that was following from it. It's true that epidemiology is insensitive, and if there was a cluster there we would have a big chance of, A, detecting that it was there and, B, then explaining why it was there. But I think that most of the environmental cancers that are caused are not in the form of these little clusters, that they are in the form of one or two cases here or there, and that the other side of the coin is that, by statistics, we can show that there will be apparently statistically significant clusters which will occur by chance.

And probability theory can show you just how many those would have to be. Let's say take Los Angeles, which has 1,300 census tracts in it. In there we tracked 50 different kinds of cancers. And the chance that a particular census track will be free of a statistically significant cancer cluster is almost 50:50.

FLATOW: All right. I'm going to have--let me--I'm sorry. I have to stop for a break here and pay some bills, so don't go away. We'll be right back after this short break and talk lots more and finish these thoughts and take your phone calls, so don't go away. We'll be right back.

I'm Ira Flatow and this is TALK OF THE NATION/SCIENCE FRIDAY from NPR News.

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FLATOW: Welcome back to TALK OF THE NATION/SCIENCE FRIDAY. I'm Ira Flatow. A brief program note: Join guest host Melinda Penkava and guests on Monday's TALK OF THE NATION in this hour as they discuss whether the man nominated to head the FBI can restore its once-proud reputation.

We're talking this hour about investigating cancer clusters with my guests: David Ozonoff, professor and chair of the Department of Environmental Health at Boston University; Raymond Neutra, chief of the Division of Environmental & Occupational Disease Control at California Department of Health Services; and Mary Guinan of the Nevada state health officer--she is the Nevada state health officer. Our number is 1 (800) 989-8255.

And, Dr. Neutra, you were making a point that I interrupted.

Dr. NEUTRA: Yeah. Dr. Ozonoff made the very good point that epidemiology doesn't have a very good detection limit. And so the way we try to get around that is study a problem by looking at many towns, not just one. So, for example, there's a concern that the use of pesticides might produce childhood leukemia, so our department is looking at the entire state and looking at all the cases of leukemia to see whether in children they are occurring more likely in agricultural areas, near the kinds of pesticides that have been suspected, rather than trying to go to one little town and hope to answer the question that way.

FLATOW: Would you have to look for a certain level of exposure to that pesticide to make you believe it's involved?

Dr. NEUTRA: Ideally, you would like to be able to measure either in the population or in the environment what kind of levels are there. And in our study we have access to the pounds of different kind of pesticide used in different parts of the state, and so that's our approximation to that issue of dose.

FLATOW: 1 (800) 989-8255 is our number. Let's go...

Dr. GUINAN: I'd like to make a comment about...

FLATOW: Sure.

Dr. GUINAN: ...the insensitivity of epidemiology.

FLATOW: Go ahead, Mary Guinan.

Dr. GUINAN: This is Mary Guinan.

FLATOW: Yeah.

Dr. GUINAN: I think that there are some situations in which it's quite sensitive, and so I wouldn't make that global comment. But when we're searching for something, if we looked at it in a different way and said, for example, that we had a known exposure, like the atomic bomb dropping in Japan, then that population is followed. One of the things about the population in Japan at that time is that it was stable and one could follow the disease in a very--just as we would consider a cohort. We followed that cohort and saw that there was an increase in leukemia in that population from an environmental hazard, which is radiation.

Now if something like that happened in the United States--let's say there was a toxic exposure in Chicago in 1980, in which there was radiation or something that could cause leukemia, hit in one day or over a one-week period. And then all those people--nobody knew it, and then all those people may have stayed in Chicago; a large proportion of them probably are not in Chicago. And so when their cancer or leukemia is reported, it would be reported where they reside at the time of their diagnosis. So if they're living in Texas or New York or--so we would--that's why the cluster would be hidden. You see the problem?

FLATOW: Yeah. Yeah. 'Cause they moved out of town.

Dr. GUINAN: Because we don't know what the exposure is.

FLATOW: They moved out of town, and some people may have moved in town...

Dr. GUINAN: Right. Right.

FLATOW: ...from some other place...

Dr. GUINAN: Exactly.

FLATOW: ...and brought it with them.

Dr. GUINAN: Right.

FLATOW: Yeah.

Dr. GUINAN: So that--the problem is that we track the cancer, we know where the cancers are when they are diagnosed. We do not know what the exposure of these people were prior to diagnosis.

FLATOW: Do you think, then--and you were talking about this earlier. Do you think if you had a huge national database of everybody's travels and if they were diagnosed with a cancer, where they'd been their whole life, that was available, you know, to epidemiologists you could get a better picture of a cluster?

Dr. GUINAN: Well, there's no doubt. I'm not sure we'd be any closer to an answer...

FLATOW: Yeah.

Dr. GUINAN: ...because it's very complicated, and we don't really have any evidence that any environmental agent except the radiation really causes excess leukemia. And for 20 years, more than 20 years, clusters have been investigated, especially clusters of childhood diseases, because the--of cancers, because the exposure period is much shorter. You look from the time of conception to the time of diagnosis, and in children it's shorter. And perhaps you could find something. Well, these clusters were investigated with great vigor, looking for either an infectious agent that might cause this or an environmental agent. And for several decades this has been going on, and then there really hasn't either--this hasn't resulted in either an infectious ideology or an environmental ideology.

Dr. OZONOFF: I don't think--yeah.

Dr. GUINAN: So that's why the investigation of these clusters fell out of--people thought maybe this was the way we could find, you know, a clue, a hypothesis to test, of what was causing these leukemias. And that hasn't happened.

Dr. OZONOFF: You know, the fact that we haven't been able to nail down these clusters, with some exceptions--not only the one that Dr. Neutra mentioned, but I would add the Woburn leukemia cluster, which was investigated not by me but by my colleagues at Harvard as being another case where an environmental cluster has been associated fairly strongly with an environmental exposure, and not everybody agrees with that, but I think it's a good example. But for the last 20, 30, 40 years, we've been really investigating these clusters with exactly the same techniques, very old techniques. We've been turning the same old rusty crank on the same old rusty machine. And we don't really have the methods yet--although I think they're starting to be developed--that would allow us to look, you know, more carefully at these clusters and have some chance of getting things.

But I agree with your example of the atomic bomb, and it just goes to show you that it takes an atomic bomb in order to be able to see these clusters.

Dr. GUINAN: Well, I think that we also have new technology that we're employing in this investigation in Fallon. And I think that's extremely important. First of all, it is assumed that one of the things that happens before leukemia occurs is there's been a genetic change to allow the cancer cells to reproduce. And that genetic change, is it caused by an agent? And how would we figure that out? Well, the human genome has been mapped now, and there've been great advances in genetics. And so one of the questions is, could we look at a cluster now and find something very specifically that is unique to this cluster, and then trace backwards to see what may have caused that. And we would come up with at least a hypothesis on what has caused the cluster.

FLATOW: You mean possibly a genetic susceptibility, and all these people have a common genetic defect?

Dr. GUINAN: No, if the exposure--let's say there was an exposure, whethe... (mindfully.org note: unfortunately, the text did not continue)

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