Do Cancer Cluster Really Exist?

1. Do Cancer Cluster Really Exist?

2. Definitions Are Important • Robert N. Hoover, M.D National Cancer Institute defines a cancer cluster as • “the occurrence of a greater than expected number of cases of a particular disease within a group of people, a geographic area, or a period of time."

3. Do Cancer Cluster Exist? • If we mean any group of cancers that have a common cause - Yes • Clusters have been found in people who share the same ancestry, in people who share the same occupation, and in people who share some other common trait such as smoking. • If we mean an unusually high number of cancer cases found in a defined geographic area, assumed to be caused by the presence of some carcinogen in the ambient environment. – Probably not • Even if such a cluster exists, • it is virtually impossible to properly validate it or to distinguish it from clusters that are due to purely to chance

4. What Do The Experts Say • Paraphrased quotes from witnesses testifying in 2001 before the Senate Cancer Coalition. • Robert N. Hoover, M.D., Director, Epidemiology and Biostatistics National Cancer Institute • David W. Fleming, M.D., Centers for Disease Control and Prevention • David A. Savitz, Professor and Chair in Epidemiology, University of North Carolina; • Sue-Min Lai, Ph.D., Associate Professor for Preventive Medicine, University Medical Center, University of Kansas; • William Wright, Ph.D., Chief, Cancer Surveillance Section, California Department of Health Services.

5. Robert N. Hoover • Investigating small disease clusters usually does not yield definitive results because cancer resulting from an environmental exposure may take many years to appear and populations in a particular geographic setting are often in flux. • David Fleming • 85-90 per cent of cancer cluster investigations do not find evidence of increased cancer risk. • Purely random events also cluster by chance, and statistical tests cannot separate observed clusters caused by chance from those due to an unrecognized common cause.

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

7. Sue-Min Lai • Most cancer cluster investigations conducted to date have not reached the feasibility stage. The following points make disease cluster investigations problematic. Geographic boundaries for a cluster study are influenced by the observed result and may be in error. The effect of population emigration and immigration will dilute disease clusters with a specific localized cause and diminish their detection by geographical studies. • William E. Wright • Studies of cancer clusters to identify an environmental cause of cancer in a selected neighborhood are almost certainly doomed to failure

8. Fear caused by the perception of cancer clusters is real • To quote David Fleming • There are few things more frightening to a community than the notion that an unseen killer is lurking in its midst. Such is the fear inspired by the belief that cancer is disproportionately striking down the people in a town.

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

10. Southside Makes National News Poisoned Schools? Schools Near Toxic Waste Sites are Making Children Sick By 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.

11. I am beyond furious after attending a meeting at Southside High School on May 2. I was so insulted by the "answers" given by the panel of "experts" that ran the meeting that evening. We were told everything was safe, but there were no answers about why children are getting sick. • Why are they developing cancer and other illnesses that normally could not be found in such concentrations in an area as small as Elmira's Southside? • The community itself needs to become so much louder. We cannot allow any cover-ups. What was in a report that was supposedly detailed in 1997? In the meantime, children are developing thyroid problems, diseases of the bone marrow, cancer, skin diseases and stomach and colon problems. And those are only the problems I heard that evening. • How many children are being treated for what may appear to be a fairly normal problem, but may have been brought on by whatever is in the soil, water and air? • And what about the surrounding neighborhoods? How many people have become sick and have died needlessly? • There has to be an answer. Until we as a family can figure out a suitable alternative, we are taking our daughter out of school near the end of her junior year.

12. SOUTHSIDE HIGH SCHOOLDraft for Public CommentU.S. Department of Health & Human Services Public Health ServiceAgency for Toxic Substances and Disease Registry • “The NYS DOH looked at the overall time period since the opening of Southside High School, and did not find an unusual pattern of cancer among current and former students, or among children living in the area served by the school. The numbers and types of cancers diagnosed were similar to what would be expected for this age group.”

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

16. Why Is This Seemingly Simple Task So Hard • Problems Defining the Relevant Cancer Cases Do you include? • All cases currently living in a geographic area • What about newcomers • What about people who have moved away • Everybody who has ever lived in a geographic area • How far back into the past is relevant • Example, a person is living in an area with a high rate of cancer and they moved there 5 years ago from an area with a high rate of cancer. To which population/area do you assign their cancer?

17. Problems Defining The Relevant Geography • Using predefined political or administrative geographic areas such as zipcodes makes no sense as the geographic area used to determine the affected population has no relationship to the suspected exposure

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

19. Zipcode 17643 Zipcode 17644 How Do You Handle This Situation

20. Is This • 2 cases in zipcode 17644 and 3 cases in zipcode 17643 or 5 cases clustered in their own area • If 5 cases clustered in their own area, how do you draw the area to determine the population to be associated with the cancer cases to calculate the rate. • May get substantially different results using the dashed as opposed to the dotted geographic area and these are only 2 out of an infinite set of areas you could draw. • If after the fact you draw areas around clusters designed to pack them in, you naturally get exaggerated rates.

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

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

23. From Me • There is no scientific way to select the cancer cases to be included in the cluster or to define the population or the geographic area to be used to define the cluster. • Inevitably the cluster is measured using arbitrary methods.

24. Lets Look More Closely At Random Distributions Over Space

25. If you throw confetti in the air and it lands on the floor does it look like this 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?

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

27. 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

29. Like confetti thrown on the floor clustering and linear structures are the expected result of a random distribution over space • Easy to draw clusters large and small • Easy to find linear structures in the data. The diagram shows only a few of the many clusters that could be identified. • Not surprising that there will be instances where clusters center around a factory site or some other assumed source of pollution, or where linear clusters appear to follow a river, highway, pipeline, or transmission line.

30. 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?

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

34. With 25 cells only 1 of 25 cells, 4% of the cells, is 150% more than the expected value of 16. • With 100 cells 12 of 100 or 12% of the cells, are 150% more than the expected value of 4. • With 25 cells the largest difference is 150% of the expected value. With 100 cells the largest difference is 225% of the expected value.

35. As the geographic areas get smaller the number of areas that deviate significantly from the expected increases and the magnitude of the deviation increases.

36. How To Identify A Real Cancer Cluster • If A causes B then wherever you find A you will tend to find B. • If A causes B then more A will tend to cause more B

37. Not logical that minute exposure to a chemical in one location causes cancer but massive exposure to the same chemical in another location doesn’t. • Not logical that short term exposure to a chemical causes cancer but long term exposure doesn’t.

38. In short, you would see a pattern that would be consistent and would persist over time and space. • This is not what is seen in virtually every neighborhood cancer cluster scare.