Interpreting epidemiologic research: lessons from studies of childhood cancer.

In recent years, the public has shown concern about trends in incidence rates, the occurrence of clusters, and the role of certain environmental exposures in the cause of childhood cancers. A frontpage news story in the New York Times1 stimulated a dramatic upswing of public anxiety about these issues. Hearings by the US Senate Environment and Public Works Committee on a cluster of 11 childhood acute lymphoblastic leukemia (ALL) cases (since increased to 13) among the 8200 residents of a town in Nevada over a 3-year period led to a featured article in USA Today2 describing legislation under consideration to enhance the federal government’s role in responding to apparent cancer outbreaks in US communities. Compared with 1.22 million cancers (excluding non-melanoma skin cancers) diagnosed annually among adults in the United States (corresponding to an average annual incidence rate for all cancers of 398 per 100 000 person-years),3 there are only 8700 diagnosed per year among children younger than 15 years and 12 400 among children and adolescents younger than 20 years (corresponding to average annual incidence rates of 13.4 per 100 000 and 14.9 per 100 000 person-years, respectively).4 Carcinomas predominate among adults, and the major pediatric tumors are nonepithelial. The most common pediatric neoplasms are the leukemias (representing 30.2% of all cancers diagnosed in children younger than 15 years), brain and central nervous system cancers (21.7%), and lymphomas (10.9%); these 3 categories (together constituting 63%) and the remaining 37% of pediatric malignancies are characterized by substantial histologic and biological diversity.5–7 Instead of the anatomic site-based categories used for adult malignancies, a more appropriate classification system developed for pediatric neoplasms8 was recently updated and designated as the International Classification of Childhood Cancer.9 This article includes 3 components. The first section focuses on terminology and criteria to evaluate whether statistical associations between risk factors and childhood cancer are causal in nature. The second section suggests a general approach for investigating possible pediatric cancer clusters. The third section considers how distinctive patterns and trends can be translated into new etiologic leads and summarizes potential causal factors (Tables 1–4).