Do Cancer Cluster Do Cancer Cluster Really Exist?Really Exist?

Definitions Are ImportantDefinitions Are Important

►Robert N. Hoover, M.D National Cancer Robert N. Hoover, M.D National Cancer Institute defines a cancer cluster asInstitute defines a cancer cluster as

““the occurrence of a greater than the occurrence of a greater than expected number of cases of a particular expected number of cases of a particular disease within a group of people, a disease within a group of people, a geographic area, or a period of time."geographic area, or a period of time."

Do Cancer Cluster ExistDo Cancer Cluster Exist??► If we mean any group of cancers that If we mean any group of cancers that

have a common cause - Yeshave a common cause - Yes Clusters have been found in people who share the same Clusters have been found in people who share the same

ancestry, in people who share the same occupation, and in ancestry, in people who share the same occupation, and in people who share some other common trait such as people who share some other common trait such as smoking.smoking.

► If we mean an unusually high number of If we mean an unusually high number of cancer cases found in a defined cancer cases found in a defined geographic area, assumed to be caused geographic area, assumed to be caused by the presence of some carcinogen in by the presence of some carcinogen in the ambient environment. – Probably the ambient environment. – Probably notnot

► Even if such a cluster exists,Even if such a cluster exists, it is virtually impossible to properly validate it or to it is virtually impossible to properly validate it or to

distinguish it from clusters that are due to purely to chance distinguish it from clusters that are due to purely to chance

What Do The Experts SayWhat Do The Experts Say► Paraphrased quotes from witnesses Paraphrased quotes from witnesses

testifying in 2001 before the Senate testifying in 2001 before the Senate Cancer Coalition. Cancer Coalition.

Robert N. Hoover, M.D., Director, Epidemiology Robert N. Hoover, M.D., Director, Epidemiology and Biostatistics National Cancer Institute and Biostatistics National Cancer Institute

David W. Fleming, M.D., Centers for Disease David W. Fleming, M.D., Centers for Disease Control and Prevention Control and Prevention

David A. Savitz, Professor and Chair in David A. Savitz, Professor and Chair in Epidemiology, University of North Carolina; Epidemiology, University of North Carolina;

Sue-Min Lai, Ph.D., Associate Professor for Sue-Min Lai, Ph.D., Associate Professor for Preventive Medicine, University Medical Center, Preventive Medicine, University Medical Center, University of Kansas; University of Kansas;

William Wright, Ph.D., Chief, Cancer Surveillance William Wright, Ph.D., Chief, Cancer Surveillance Section, California Department of Health Section, California Department of Health Services.Services.

► Robert N. HooverRobert N. Hoover Investigating small disease clusters usually does Investigating small disease clusters usually does

not yield definitive results because cancer not yield definitive results because cancer resulting from an environmental exposure may resulting from an environmental exposure may take many years to appear and populations in a take many years to appear and populations in a particular geographic setting are often in flux.particular geographic setting are often in flux.

► David FlemingDavid Fleming 85-90 per cent of cancer cluster investigations do 85-90 per cent of cancer cluster investigations do

not find evidence of increased cancer risk.not find evidence of increased cancer risk.

Purely random events also cluster by chance, Purely random events also cluster by chance,

and statistical tests cannot separate observed and statistical tests cannot separate observed clusters caused by chance from those due to an clusters caused by chance from those due to an unrecognized common cause. unrecognized common cause.

►David A. SavitzDavid A. Savitz Studying cancer clusters over short periods of Studying cancer clusters over short periods of

time and by locations have not been time and by locations have not been successful because 1) most environmental successful because 1) most environmental exposures happen very slowly, often over exposures happen very slowly, often over decades, and thus, an elevated cancer rate decades, and thus, an elevated cancer rate for 6 months or 1 year is not likely to point to for 6 months or 1 year is not likely to point to some specific, identifiable cause, 2) causes of some specific, identifiable cause, 2) causes of cancer operate over many years, so that cancer operate over many years, so that clustering at the time of diagnosis does not clustering at the time of diagnosis does not correspond to clustering at the time when correspond to clustering at the time when they were actually caused, 3) exposures that they were actually caused, 3) exposures that tend to cluster in time and space may well tend to cluster in time and space may well not be the dominant causes of cancer not be the dominant causes of cancer

► Sue-Min LaiSue-Min Lai Most cancer cluster investigations conducted to Most cancer cluster investigations conducted to

date have not reached the feasibility stage. The date have not reached the feasibility stage. The following points make disease cluster following points make disease cluster investigations problematic. Geographic investigations problematic. Geographic boundaries for a cluster study are influenced by boundaries for a cluster study are influenced by the observed result and may be in error. The the observed result and may be in error. The effect of population emigration and immigration effect of population emigration and immigration will dilute disease clusters with a specific will dilute disease clusters with a specific localized cause and diminish their detection by localized cause and diminish their detection by geographical studies.geographical studies.

► William E. WrightWilliam E. Wright Studies of cancer clusters to identify an Studies of cancer clusters to identify an

environmental cause of cancer in a selected environmental cause of cancer in a selected neighborhood are almost certainly doomed to neighborhood are almost certainly doomed to failurefailure

Fear caused by the perception Fear caused by the perception of cancer clusters is real of cancer clusters is real

► To quote David FlemingTo quote David Fleming There are few things more frightening There are few things more frightening

to a community than the notion that an to a community than the notion that an unseen killer is lurking in its midst. Such unseen killer is lurking in its midst. Such is the fear inspired by the belief that is the fear inspired by the belief that cancer is disproportionately striking cancer is disproportionately striking down the people in a town. down the people in a town.

Southside High SchoolSouthside High SchoolOne of many cancer cluster One of many cancer cluster scares around the countryscares around the country

► "From the high rates of cancer at a "From the high rates of cancer at a high school in Elmira to the alarmingly high school in Elmira to the alarmingly high breast cancer rates on Long high breast cancer rates on Long Island, communities in New York and Island, communities in New York and around the country people want to around the country people want to know what's making them sick - it's know what's making them sick - it's time for us to step up our efforts to find time for us to step up our efforts to find the answers," Clinton said last week.the answers," Clinton said last week.

Southside Makes National Southside Makes National NewsNews

Poisoned Schools?Schools Near Toxic Waste Sites are Making Children SickBy Michele Norris

An Elmira mother and her son will appear at 9 a.m. today on MSNBC's "The Hour Show" to discuss the state's cancer investigation at Southside High School.

The Patros family has also been contacted by ABC's "Good Morning America" to discuss their views about the investigation, said husband and father, Andy Patros, who remained in Elmira.

            

► I am beyond furious after attending a meeting at Southside I am beyond furious after attending a meeting at Southside High School on May 2. I was so insulted by the "answers" High School on May 2. I was so insulted by the "answers" given by the panel of "experts" that ran the meeting that given by the panel of "experts" that ran the meeting that evening. We were told everything was safe, but there were no evening. We were told everything was safe, but there were no answers about why children are getting sick.answers about why children are getting sick.

► Why are they developing cancer and other illnesses that Why are they developing cancer and other illnesses that normally could not be found in such concentrations in an area normally could not be found in such concentrations in an area as small as Elmira's Southside?as small as Elmira's Southside?

► The community itself needs to become so much louder. We The community itself needs to become so much louder. We cannot allow any cover-ups. What was in a report that was cannot allow any cover-ups. What was in a report that was supposedly detailed in 1997? In the meantime, children are supposedly detailed in 1997? In the meantime, children are developing thyroid problems, diseases of the bone marrow, developing thyroid problems, diseases of the bone marrow, cancer, skin diseases and stomach and colon problems. And cancer, skin diseases and stomach and colon problems. And those are only the problems I heard that evening.those are only the problems I heard that evening.

► How many children are being treated for what may appear to How many children are being treated for what may appear to be a fairly normal problem, but may have been brought on by be a fairly normal problem, but may have been brought on by whatever is in the soil, water and air?whatever is in the soil, water and air?

► And what about the surrounding neighborhoods? How many And what about the surrounding neighborhoods? How many people have become sick and have died needlessly?people have become sick and have died needlessly?

► There has to be an answer. Until we as a family can figure out There has to be an answer. Until we as a family can figure out a suitable alternative, we are taking our daughter out of a suitable alternative, we are taking our daughter out of school near the end of her junior year.school near the end of her junior year.

SOUTHSIDE HIGH SCHOOLSOUTHSIDE HIGH SCHOOLDraft for Public CommentDraft for Public Comment

U.S. Department of Health & Human Services U.S. Department of Health & Human Services Public Health ServicePublic Health Service

Agency for Toxic Substances and Disease Agency for Toxic Substances and Disease RegistryRegistry

► ““The NYS DOH looked at the overall time The NYS DOH looked at the overall time period since the opening of Southside High period since the opening of Southside High School, and did not find an unusual pattern School, and did not find an unusual pattern of cancer among current and former of cancer among current and former students, or among children living in the students, or among children living in the area served by the school. The numbers area served by the school. The numbers and types of cancers diagnosed were and types of cancers diagnosed were similar to what would be expected for this similar to what would be expected for this age group.”age group.”

Cancer Maps, A New Tool To Cancer Maps, A New Tool To Scare The Daylights Out Of Scare The Daylights Out Of

PeoplePeople

Why Is This Seemingly Simple Why Is This Seemingly Simple Task So HardTask So Hard

► Problems Defining the Relevant Cancer Problems Defining the Relevant Cancer Cases Cases

Do you include?Do you include?

► All cases currently living in a geographic areaAll cases currently living in a geographic area What about newcomersWhat about newcomers What about people who have moved awayWhat about people who have moved away

► Everybody who has ever lived in a geographic areaEverybody who has ever lived in a geographic area How far back into the past is relevantHow far back into the past is relevant

► Example, a person is living in an area with a high rate Example, a person is living in an area with a high rate of cancer and they moved there 5 years ago from an of cancer and they moved there 5 years ago from an area with a high rate of cancer. To which area with a high rate of cancer. To which population/area do you assign their cancer? population/area do you assign their cancer?

Problems Defining The Relevant Problems Defining The Relevant GeographyGeography

►Using predefined political or Using predefined political or administrative geographic areas such administrative geographic areas such as zipcodes makes no sense as the as zipcodes makes no sense as the geographic area used to determine the geographic area used to determine the affected population has no relationship affected population has no relationship to the suspected exposureto the suspected exposure

Examine the map below you see Examine the map below you see adjacent zipcodes with high and low adjacent zipcodes with high and low

ratesrates

How Do You Handle This How Do You Handle This SituationSituation

Zipcode 17643

Zipcode17644

Is ThisIs This► 2 cases in zipcode 17644 and 3 cases in zipcode 2 cases in zipcode 17644 and 3 cases in zipcode

17643 or 5 cases clustered in their own area17643 or 5 cases clustered in their own area

► If 5 cases clustered in their own area, how do you If 5 cases clustered in their own area, how do you draw the area to determine the population to be draw the area to determine the population to be associated with the cancer cases to calculate the associated with the cancer cases to calculate the rate.rate.

May get substantially different results using the dashed May get substantially different results using the dashed as opposed to the dotted geographic area and these are as opposed to the dotted geographic area and these are only 2 out of an infinite set of areas you could draw.only 2 out of an infinite set of areas you could draw.

If after the fact you draw areas around clusters designed If after the fact you draw areas around clusters designed to pack them in, you naturally get exaggerated rates.to pack them in, you naturally get exaggerated rates.

From the National Cancer From the National Cancer InstituteInstitute

► Before a cluster can be considered "true," Before a cluster can be considered "true," epidemiologists must show that the number epidemiologists must show that the number of cancer cases which have occurred is of cancer cases which have occurred is significantly greater than the number of cases significantly greater than the number of cases that would be expected, given the age, that would be expected, given the age, gender, and racial distribution of the group of gender, and racial distribution of the group of people at risk of developing the disease. people at risk of developing the disease. However, it is often very difficult, if not However, it is often very difficult, if not impossible, to accurately define the group of impossible, to accurately define the group of people who should be considered "at risk." people who should be considered "at risk."

From the National Cancer From the National Cancer InstituteInstitute

► One of the greatest pitfalls of defining One of the greatest pitfalls of defining clusters is the tendency to extend the clusters is the tendency to extend the geographic borders of the cluster to include geographic borders of the cluster to include additional cases of the suspected disease as additional cases of the suspected disease as they are discovered. The tendency to define they are discovered. The tendency to define the borders of a cluster on the basis of where the borders of a cluster on the basis of where one knows the cases are located, rather than one knows the cases are located, rather than to first define the population and then to first define the population and then determine if the number of cancers is determine if the number of cancers is excessive, creates many "clusters" that are excessive, creates many "clusters" that are not genuine.not genuine.

From MeFrom Me

►There is no scientific way to select the There is no scientific way to select the cancer cases to be included in the cancer cases to be included in the cluster or to define the population or cluster or to define the population or the geographic area to be used to the geographic area to be used to define the cluster. define the cluster.

► Inevitably the cluster is measured Inevitably the cluster is measured using arbitrary methods.using arbitrary methods.

Lets Look More Closely At Lets Look More Closely At Random Distributions Over Random Distributions Over

SpaceSpace

If you throw confetti in the air and it If you throw confetti in the air and it lands on the floor does it look like lands on the floor does it look like

thisthis

Most people understand that the confetti will fall in clumps with bare spaces between the clumps. Why should randomly distributed cancer cases look any different?

To illustrate, try this Excel exercise to To illustrate, try this Excel exercise to generate and examine random distribution generate and examine random distribution over space. Use Tools/Data Analysis/Random over space. Use Tools/Data Analysis/Random Number Generator to generate a Uniform Number Generator to generate a Uniform distribution of 2 sets of 400 random numbers distribution of 2 sets of 400 random numbers between 0 and 100between 0 and 100

Make an xy scatter diagram using one variable as the x axis and the other as the y axes. You now have 400 randomly distributed dots over a 100 by 100 graphical space. Below is one result

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Like confetti thrown on the floor Like confetti thrown on the floor clustering and linear structures are the clustering and linear structures are the

expected result of a random distribution expected result of a random distribution over spaceover space

► Easy to draw clusters large and smallEasy to draw clusters large and small

► Easy to find linear structures in the data. Easy to find linear structures in the data. The diagram shows only a few of the many The diagram shows only a few of the many clusters that could be identified.clusters that could be identified.

► Not surprising that there will be instances Not surprising that there will be instances where clusters center around a factory site where clusters center around a factory site or some other assumed source of or some other assumed source of pollution, or where linear clusters appear pollution, or where linear clusters appear to follow a river, highway, pipeline, or to follow a river, highway, pipeline, or transmission line.transmission line.

We can add grid lines to the diagram to create large and small geographic areas. How will deviation from the expected value be affected by the size of the geographic area?

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As geographic areas get smaller, deviation from the expected get larger and more common

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Frequency Chart 25 Cells

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Frequency Chart100 Cells

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► With 25 cells only 1 of 25 cells, 4% of With 25 cells only 1 of 25 cells, 4% of the cells, is 150% more than the the cells, is 150% more than the expected value of 16.expected value of 16.

► With 100 cells 12 of 100 or 12% of With 100 cells 12 of 100 or 12% of the cells, are 150% more than the the cells, are 150% more than the expected value of 4.expected value of 4.

► With 25 cells the largest difference is With 25 cells the largest difference is 150% of the expected value. With 150% of the expected value. With 100 cells the largest difference is 100 cells the largest difference is 225% of the expected value. 225% of the expected value.

As the geographic areas get As the geographic areas get smaller the number of areas smaller the number of areas

that deviate significantly that deviate significantly from the expected increases from the expected increases

and the magnitude of the and the magnitude of the deviation increases.deviation increases.

How To Identify A Real Cancer How To Identify A Real Cancer ClusterCluster

► If A causes B then wherever you find A If A causes B then wherever you find A you will tend to find B.you will tend to find B.

► If A causes B then more A will tend to If A causes B then more A will tend to cause more Bcause more B

►Not logical that minute exposure to a Not logical that minute exposure to a chemical in one location causes cancer chemical in one location causes cancer but massive exposure to the same but massive exposure to the same chemical in another location doesn’t.chemical in another location doesn’t.

►Not logical that short term exposure to Not logical that short term exposure to a chemical causes cancer but long a chemical causes cancer but long term exposure doesn’t.term exposure doesn’t.

► In short, you would see a pattern that In short, you would see a pattern that would be consistent and would persist would be consistent and would persist over time and space.over time and space.

►This is not what is seen in virtually This is not what is seen in virtually every neighborhood cancer cluster every neighborhood cancer cluster scare.scare.