Recently we read with concern about an apparent cluster of Ewing sarcoma cases, and possibly other rare pediatric cancers, in Ladera Ranch. We are writing as two epidemiologists who seek to understand the causes of childhood cancers to offer our advice and expertise to the community and the authorities conducting the investigations now under way.
First, it is important to understand that the number of cases alone does not indicate an increased rate. To determine the rate of Ewing sarcoma in Ladera Ranch children requires establishing the population denominator, i.e. the number of children at risk of the disease.
Media reports suggest the first Ewing sarcoma case in Ladera Ranch was diagnosed in 2007, thus the denominator will include far more people than just the present pediatric population of the town. Investigators will calculate the rate of Ewing sarcoma in Ladera Ranch and compare it to the rate in all of Orange County or California. It is not guaranteed that properly calculated population rates will support the community’s perception of a cluster.
Should the rate of Ewing sarcoma be found to be elevated in Ladera Ranch we do support an investigation of potential causes in order to allay community concerns, but it is important to manage expectations about what cluster investigations can and cannot reveal.
In 2012, scientists reviewing the prior 20 years of state and federal investigations put it succinctly: “It is fair to state that extensive efforts to find causes of community cancer clusters have not been successful.”
Subsequently they made recommendations on how to improve investigations, for instance by incorporating modern innovations like tumor sequencing, which we endorse.
No amount of scientific sophistication, however, can overcome the fundamental problem facing any cluster investigation, namely the small absolute numbers of cases. At the turn of the century there were up to 16 cases of childhood leukemia diagnosed in Fallon, Nevada versus 1 or 2 expected. Despite spending millions of dollars investigating this highly improbable event the authorities found no clear cause.
The community of Ladera Ranch is particularly concerned about pesticide use as a potential cause of Ewing sarcoma.
We have published studies examining pesticide exposure and some childhood cancers and agree that they may contribute to causation of a number of cancer types, but Ewing sarcoma is not one of them. The evidence base connecting environmental chemicals of any kind to Ewing sarcoma is very thin. It is important to understand that even if pesticide exposure doubled or tripled the incidence of Ewing sarcoma that is not likely to result in a “cluster.”
At its peak in adolescence the rate of Ewing sarcoma is about 7 cases per million children and three times that rate is still exceedingly rare. Pesticides are used in many other areas of Orange County and California (the US state with highest pesticide usage, particularly in the Central Valley) without having led to other apparent clusters, which also argues against them being a strong cause of Ewing sarcoma.
None of this is to say that pesticides are harmless or that they should continue to be used in Ladera Ranch, but we think it very unlikely any investigation is going to provide definitive proof that pesticides caused these cases of Ewing sarcoma among the town’s children.
The most valuable and informative part of the investigation will instead be the comparison of the Ladera Ranch cases to the larger Ewing sarcoma population. Do they look the same or different in terms of demographics, age at diagnosis, location of tumor, etc? Particularly if it is possible to sequence their tumor and normal DNA then investigators will be able to say if anything is out of the ordinary among patients in the town.
It is natural for people to feel that there must be a cause behind uncommon occurrences but this instinct is frequently wrong. It is human nature to draw a circle around an apparent cluster of events that appears nonrandom, which can lead to what is commonly called the “Texas sharpshooter” fallacy.
As two scientists who study probability we can tell you that coincidence can, in fact, be the reason for an apparent cluster. This is because in a country the size of the United States it is likely that cases will randomly occur closely in time and space somewhere over the course of a few decades, even if it is very improbable to have happened in Ladera Ranch specifically.
We look forward to a thorough scientific investigation of Ewing sarcoma and other pediatric cancers in Ladera Ranch and hope the community understands the limits of what science can tell them about the reasons this awful disease befell their children.
Dr. Logan G. Spector is professor of pediatrics at the University of Minnesota Medical School. Dr. Joseph Wiemels is professor of population and public health sciences at the Keck School of Medicine of USC. They are the chair and a member, respectively, of the Childhood Cancer and Leukemia International Consortium.