Cohort profile: the International Childhood Cancer Cohort Consortium (I4C).

Globally, a number of large infant/child prospective studies have been launched to examine environmental and genetic determinants of common diseases of children, such as asthma, developmental delay and behaviour abnormalities, as well as the consequences of early exposure for adult diseases. While several of these studies are relatively very large—over 100 000 subjects—and are adequately powered to examine their principal outcomes of interest, none of the individual studies are of sufficient size to examine the relationship between exposures they are measuring and rare diseases such as childhood cancer. To date, the few established risk factors for specific forms of childhood cancer have largely been identified in case-control studies. Yet, despite many such investigations evaluating postulated risk factors for paediatric malignancies during the past five decades, few consistently established aetiologic factors are known. Recent review papers have summarized many promising hypotheses, including pre-natal and post-natal exposure to pesticides, maternal and early infancy dietary factors, paternal pre-conception occupational exposures and smoking, the interplay of maternal or early postnatal immune system handling of common infections, determinants of high birth weight and other factors. Employment of prospective cohort follow-up of children and adolescents from pregnancy or birth using cohort or nested case-cohort designs, in conjunction with prospective biological sample collection, offers promising opportunities for advancing knowledge of aetiology. This is a result of improved assessment of parental and early life exposures, measurement of biological samples for pre-diagnostic effects, clarification of the temporal relationship between exposure and outcome, reduction of differential recall between parents of cases vs controls and the prospect of understanding the determinants of selection bias. The concept of bringing the various cohorts of infants and children together in an international collaboration arose during planning for the National Children’s Study (NCS), a childhood cohort study in the United States of 100 000 participants. Participants at a 2004 workshop convened to consider whether this cohort would be of sufficient size to include cancer as a feasible outcome; they concluded that this study would have insufficient power for this purpose due to the rarity of all forms of childhood cancer. However, a collaboration of the existing and planned large childhood cohorts globally might provide the power necessary to obtain prospective evidence on potential causes of childhood cancer. This idea was developed further and a proposal was presented to the National Institute for Child Health and Human Development (NICHD), National Cancer Institute (NCI) and the US Environmental Protection Agency (EPA). Along with funding support from the National Institute of Health’s Office of Rare Diseases, these organizations held a workshop in 2005, bringing together representatives from 11 cohorts in four continents, accounting for 700 000 children (Table 1), as well as experts in epidemiology, paediatric oncology, genetics, toxicology and other disciplines. Its purpose * Corresponding author. U.S. Environmental Protection Agency, National Center for Environmental Assessment, 1200 Pennsylvania Avenue, NW, 8623D, Washington, DC, 20460 USA. E-mail: brown.rebecca@epa.gov 1 National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. 2 Murdoch Childrens Research Institute, Melbourne, Australia. 3 National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. 4 National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. 5 National Center for Maternal and Infant Health, Peking University Health Science Center, Beijing, China. 6 Department of Epidemiology, University of California, Los Angeles, CA, USA. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org Published by Oxford University Press on behalf of the International Epidemiological Association The Author 2007; all rights reserved. Advance Access publication 25 January 2007 International Journal of Epidemiology 2007;36:724–730 doi:10.1093/ije/dyl299