Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case-control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene-environment interactions. Objectives: The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene-environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods: By September 2012, CLIC included 22 studies (recruitment period: 1962-present) from 12 countries, totaling approximately 31. 000 cases and 50. 000 controls. Of these, 19 case-control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child-parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions: CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene-environment interactions and associations among specific leukemia subtypes in different ethnic groups.
Bibliographical noteFunding Information:
Research Investigator : Daniel Sinnett (University of Montréal). Funding : Canadian Institutes of Health Research, the Cole Foundation, the Network of Applied Medical Genetics (Fonds de la recherche en santé du Québec), the Cancer Research Society Inc, the Leukemia and Lymphoma Society of Canada, Genome Quebec/Canada, Terry Fox Research Institute, and the Research Chair François-Karl-Viau in Pediatric Oncogenomics.
Research Investigator : Claire Infante-Rivard (McGill Univertsity, Montréal). Funding : National Cancer Institute of Canada and CCERN, the Medical Research Council of Canada, the Canadian Institutes of Health Research, the Fonds de la recherche en santé du Québec, the Bureau of Chronic Disease Epidemiology, Health and Welfare Canada, the Leukemia Research Fund of Canada, and the National Health and Research Development Program, Ottawa.
Two projects were initiated to demonstrate a proof of principle for pooling data within CLIC. One examined the associations between maternal vitamin and folate supplementation during pregnancy and the risk of childhood ALL and AML (supported by funding from the National Cancer Institute, NCI, USA), and the other investigated the association between two measures of fetal growth and childhood ALL (supported by funding from the Cancer Council Western Australia). These initiatives enabled CLIC to develop guidelines and procedures for requesting and pooling data, and guidelines for membership and authorship. The latter were modeled on successful consortia of adult cancers (i.e., the International Lymphoma Epidemiology Consortium, Interlymph, http://epi.grants.cancer.gov/InterLymph/ ); the International Lung Cancer Consortium, ILCCO, http://ilcco.iarc.fr/ ), and other references such as the International Committee of Medical Journal Editors ( http://www.icmje.org/ ).
Research and Clinical Investigators : Maria S. Pombo-de-Oliveira, Sergio Koifman, Fernando A. Werneck, Jane Dobbin, Mariana Emerenciano, Marcela B. Mansur, Jeniffer D. Ferreira, and Arnaldo C. Couto (Rio de Janeiro); Isis Q. Magalhães and José C. Cordoba (Brasilia); Vitória R.Pereira Pinheiro and Silvia R. Brandalise (Campinas); Imaruí Costa (Florianopolis); Mara A.D. Pianovsky, Flora M. Watanabe (Parana); Núbia Mendonça, Nilma Pimentel Brito, Eny Guimarães de Carvalho, and Ana Maria Marinho (Salvador); Virginia M. Cóser (Santa Maria); Gilberto Ramos (Belo Horizonte); Flávia Pimenta and Andreia Gadelha (Joao Pessoa); Cesar Bariani (Goiania); Marcelo S. Santos and Rosania Baseggio (Campo Grande); Alejandro Aranciba and Renato Melarangno (São Paulo). Funding : Brazilian National Research Council (CNPq), the State of Rio de Janeiro Research Foundation (FAPERJ), the Ministry of Health of Brazil, and the Swiss Bridge Foundation.
Research Investigators : Patricia Monge, Catharina Wesseling, and Timo Partanen (Universidad Nacional, Costa Rica); Anders Ahlbom and Elisabete Weiderpass (Karolinska Insitutet, Sweden), and Kenneth Cantor (National Cancer Institute, USA). Funding : Research Department of the Swedish International Development Cooperation Agency (Sida/SAREC) and National Cancer Institute, USA.
Research Investigators: Jacqueline Clavel and Jérémie Rudant (Inserm, CESP, Université Paris-Sud). Funding : ADELE : Inserm, the French Ministère de l’Environnement, the Association pour la Recherche contre le Cancer (ARC), the Fondation de France, the Fondation Jeanne Liot, the Fondation Weisbrem-Berenson, the Ligue Contre le Cancer du Val de Marne, and the Ligue Nationale Contre le Cancer. ELECTRE : Inserm, the Ministère de l’Environnement et de l’Aménagement du Territoire, the Fondation pour la Recherche Médicale, ARC, the Fondation de France, and the Institut Electicité Santé. ESCALE : Inserm, the Fondation de France, ARC, the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), the Agence Française de Sécurité Sanitaire de l’Environnement et du Travail (AFSSET), the association Cent pour sang la vie, the Institut National du Cancer (INCa), the Agence Nationale de la Recherche (ANR), and the Cancéropôle Ile de France. ESTELLE : Association Enfants et Santé, the Ligue Nationale contre le Cancer, the Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES), the Institut National du Cancer (INCa), the Cancéropôle Ile de France.
Research Investigators : John D. Dockerty, Peter G. Herbison, David C.G. Skegg, and J. Mark Elwood (University of Otago). Funding : Health Research Council of New Zealand (NZ), the NZ Lottery Grants Board, the Otago Medical School (Faculty Bequest Funds), the Cancer Society of NZ, the Otago Medical Research Foundation, and the A.B. de Lautour Charitable Trust.
Research Investigators : Beth Mueller, Parveen Bhatti, Eric Chow, Bill O’Brien, Michelle Williams, Danise Podvin, Carrie Kuehn (University of Washington). Funding : Washington State Department of Health, the Cancer Surveillance System of Western Washington part of the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, and the Fred Hutchinson Cancer Center.