Bioelectromagnetics Supplement 7:S51 ^ S59 (2005) Review Childhood Leukemia and EMF: Review of the Epidemiologic Evidence Leeka Kheifets* and Riti Shimkhada Department of Epidemiology, UCLA School of Public Health, Los Angeles, California, USA All populations are exposed to varying degrees of electromagnetic fields (EMF); in this study we consi- der only extremely low frequency (ELF) and radio frequency (RF) fields. After the first study of ELF and childhood leukemia in 1979, intensive epidemiologic investigation has sought to shed light on the potential relation between EMF and childhood leukemia. Consistent associations from epidemiologic studies and two pooled analyses have been the basis for the classification of ELF as a possible carcinogen by the International Agency for Research on Cancer (IARC). The study of RF is still in its infancy and little is known about residential RF exposure or its potential effects on childhood leukemia. The purpose of this study, presented at the WHO Workshop on Sensitivity of Children to EMF in Istanbul, Turkey in June 2004, is to review and critically assess the epidemiologic evidence on EMF and childhood leukemia. Bioelectromagnetics Supplement 7:S51–S59, 2005. ß 2005 Wiley-Liss, Inc. Key words: epidemiology; extremely low frequency EMF; radio frequency; cancer; review INTRODUCTION Childhood leukemia has remained a focal point of extensive etiologic, diagnostic, and therapeutic research since its recognition as a clinical entity over a century ago [Pinkel, 1993]. It is one of the most common cancers in children, comprising more than a third of all childhood cancers [Greenberg and Shuster, 1985]. The age standardized rate of leukemia for children younger than 15 years has been estimated to be 3.5 per 100 000 per year for females and 4.2 per 100 000 per year for males in the developed world, 2.2 per 100 000 per year for females, and 2.9 per 100 000 per year for males in the developing world [IARC, 2000]. Leukemia results from chromosomal alterations and mutations that disrupt the normal process by which lymphoid or myeloid progenitor cells differentiate. The underlying triggers for molecular damage may be inherited at conception, may occur during fetal development or during infancy (see T. Lightfoot in this issue for details). Most likely there is an accumulation of a series of detrimental genetic changes over time. Though there have been significant advances in diagnostic techniques and improvements in treatment, most of the etiology of leukemia in children is unknown. A wide variety of factors have been hypothesized to be involved in the etiology of childhood leukemia. Among environmental exposures possibly associated with childhood leukemia, ionizing radiation is a gene- rally accepted risk factor [Bhatia et al., 1999]. The list of chemical agents for which some evidence points to a link with leukemogenesis includes solvents, pesticides, tobacco smoke, and certain dietary agents. The possible role of viral or other infectious agents in triggering leukemia development has also been hypothesized [Mezei and Kheifets, 2002]. Generally accepted asso- ciations, however, explain only 10% of childhood leukemia incidence [Ichimaru et al., 1978], leaving the majority with unexplained etiology. Consistent epidemiologic evidence demonstrates a small risk of extremely low frequency (ELF) elec- tromagnetic fields (EMF) on childhood leukemia, thus leading to an International Agency for Research on Cancer (IARC) classification of ELF as a ‘‘possible’’ or 2B carcinogen in 2002. As compared to the ELF literature, research on the potential health effects of radio-frequency (RF) EMF is still in its infancy and studies to date have been uninformative. The purpose of this study is to present the epidemiologic literature on EMF and childhood leukemia, and to discuss possible ß 2005 Wiley-Liss,Inc. —————— Grant sponsor: Electric Power Research Institute (EPRI). *Correspondence to: Prof. Leeka Kheifets, Department of Epidemiology, UCLA School of Public Health, 73-284 CHS, 650 Charles E. Young Drive South, Los Angeles, CA 90095-1772. E-mail: kheifets@ucla.edu Received for review 18 September 2004; Final revision received 11 April 2005 DOI 10.1002/bem.20139 Published online 29 July 2005 in Wiley InterScience (www.interscience.wiley.com).