Parental occupational paint exposure and risk of childhood leukemia in the offspring: findings from the Childhood Leukemia International Consortium
It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring.
We obtained individual level data from 13 case–control studies participating in the Childhood Leukemia International Consortium. Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression.
Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukemia (ALL) was 0.93 [95 % confidence interval (CI) 0.76, 1.14]. Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95 % CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95 % CI 0.65, 1.41) and 1.31 (95 % CI 0.38, 4.47), respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest.
Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed.
KeywordsPaint Parental occupation Leukemia Childhood Pooled analysis Meta-analysis
Acute lymphoblastic leukemia
Acute myeloid leukemia
Australian Study of Causes of Acute Lymphoblastic Leukaemia in Children
Childhood Leukemia International Consortium
Childhood Oncology Group (Children's Cancer Group)
Epidemiological Study on Childhood Cancer and Leukemia
German Childhood Cancer Registry
International Standard Classification for Occupation
Job exposure matrix
Nationwide Registration for Childhood Haemotological Malignancies
Northern California Childhood Leukemia Study (USA)
Not else classified
New Zealand Childhood Cancer Study
Random digit dialing
Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma
United Kingdom Childhood Cancer Study
We would like to thank our dear colleague and friend, Patricia Buffler, who passed away before the submission of this manuscript. She was a founding member and Chair of CLIC as well as the driving force behind the NCCLS. She provided unconditional support to finding the causes of childhood leukemia, and her scientific leadership and guiding forces within CLIC will be remembered. The Aus-ALL consortium conducted the study and the Telethon Kids Institute (formerly Telethon Institute for Child Health Research) (TICHR), University of Western Australia, was the coordinating center. Bruce Armstrong (Sydney School of Public Health), Elizabeth Milne (TICHR), Frank van Bockxmeer (Royal Perth Hospital), Michelle Haber (Children’s Cancer Institute Australia), Rodney Scott (University of Newcastle), John Attia (University of Newcastle), Murray Norris (Children’s Cancer Institute Australia), Carol Bower (TICHR), Nicholas de Klerk (TICHR), Lin Fritschi (WA Institute for Medical Research, WAIMR), Ursula Kees (TICHR), Margaret Miller (Edith Cowan University), Judith Thompson (WA Cancer Registry) were the research investigators, Helen Bailey (TICHR) was the project coordinator, and Alison Reid (WAIMR) performed the occupational analyses. The clinical Investigators were: Frank Alvaro (John Hunter Hospital, Newcastle); Catherine Cole (Princess Margaret Hospital for Children, Perth); Luciano Dalla Pozza (Children’s Hospital at Westmead, Sydney); John Daubenton (Royal Hobart Hospital, Hobart); Peter Downie (Monash Medical Centre, Melbourne); Liane Lockwood (Royal Children’s Hospital, Brisbane); Maria Kirby (Women’s and Children’s Hospital, Adelaide); Glenn Marshall (Sydney Children’s Hospital, Sydney); Elizabeth Smibert (Royal Children’s Hospital, Melbourne); Ram Suppiah (previously Mater Children’s Hospital, Brisbane). GCCR: The German study was conducted by the nationwide German Childhood Cancer Registry (GCCR) at the Institute of Medical Biostatistics, Epidemiology and Informatics at the Johannes Gutenberg University Mainz; researchers involved were Drs Jörg Michaelis (head), Peter Kaatsch, Uwe Kaletsch, Rolf Meinert, Anke Miesner, and Joachim Schüz. NARECHEM Greek Pediatric Hematology Oncology Clinicians: Margarita Baka MD: Department of Pediatric Hematology-Oncology, “Pan.&Agl. Kyriakou” Children’s Hospital, Athens, Greece, Thivon & Levadeias, Goudi; Maria Moschovi MD: Hematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, “Aghia Sophia” General Children’s Hospital, Athens, Greece, Thivon & Papadiamantopoulou, Goudi, 11527 Athens, Greece; Sophia Polychronopoulou MD: Department of Pediatric Hematology-Oncology, “Aghia Sophia” General Children’s Hospital, Athens, Greece, Thivon & Papadiamantopoulou, Goudi, 11527 Athens, Greece; Emmanuel Hatzipantelis MD, PhD: Pediatric Hematology Oncology Unit, 2nd Pediatric Department of Aristotle University, AHEPA General Hospital, Thessaloniki, Greece, 1 St. Kyriakidi, 54636 Thessaloniki, Greece; Ioanna Fragandrea MD: Pediatric Oncology Department, Hippokration Hospital, Thessaloniki, Greece; Eftychia Stiakaki MD: Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Greece; Nick Dessypris, MSc, PhD and Evanthia Bouka, MPH: Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, 11527 Athens, Greece; Ioannis Matsoukis MD: Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, 11527 Athens, Greece. The SETIL (Italian Multicentric Epidemiological Study on Risk Factors of Childhood Leukaemia, Non-Hodgkin Lymphoma and Neuroblastoma) Working Group: Corrado Magnani and Alessandra Ranucci (Cancer Epidemiology Unit, CPO Piedmont Novara); Lucia Miligi, Alessandra Benvenuti, Patrizia Legittimo and Angela Veraldi (Occupational and Environmental Unit,ISPO, Firenze); Antonio Acquaviva (AOU Siena); Maurizio Aricò, Alma Lippi and Gabriella Bernini (AOU Meyer, Firenze); Giorgio Assennato (ARPA, Bari); Stefania Varotto and Paola Zambon (Università di Padova); Pierfranco Biddau and Roberto Targhetta (Ospedale Microcitemico, Cagliari); Luigi Bisanti and Giuseppe Sampietro (ASL di Milano); Francesco Bochicchio, Susanna Lagorio, Cristina Nuccetelli, Alessandro Polichetti and Serena Risica (ISS, Roma); Santina Cannizzaro and Lorenzo Gafà (LILT, Ragusa); Egidio Celentano (ARSan, Napoli); Pierluigi Cocco (Università di Cagliari); Marina Cuttini (IRCCS Burlo Garofolo, Trieste); Francesco Forastiere,Ursula Kirchmayer and Paola Michelozzi (Dipartimento Epidemiologia Regione Lazio, Roma); Erni Guarino (INT Napoli); Riccardo Haupt (Istituto Giannina Gaslini, Genova); Franco Locatelli (Università di Pavia and AO Bambin Gesù, Roma); Lia Lidia Luzzatto (ASL 1, Torino); Giuseppe Masera (Università Milano Bicocca, Monza); Pia Massaglia (Università di Torino); Stefano Mattioli and Andrea Pession (Università di Bologna); Domenico Franco Merlo and Vittorio Bocchini (IST, Genova); Liliana Minelli and Manuela Chiavarini (Università degli Studi di Perugia); Margherita Nardi (AOU Pisa); Paola Mosciatti and Franco Pannelli (Università di Camerino); Vincenzo Poggi (AORN Santobono – Pausilipon, Napoli); Alessandro Pulsoni (Sapienza University, Roma); Carmelo Rizzari (AO San Gerardo, Monza); Roberto Rondelli (Policlinico S.Orsola, Bologna); Gino Schilirò (Università di Catania); Alberto Salvan (IASI-CNR, Roma); Maria Valeria Torregrossa and Rosaria Maria Valenti (Università degli Studi di Palermo); Alessandra Greco, Gian Luca DeSalvo and Daniele Monetti (IOV-IRCCS, Padova); Claudia Galassi (San Giovanni Battista Hospital, Torino); Veronica Casotto (IRCCS Burlo Garofolo, Trieste); Gigliola de Nichilo (ASL BT, SPRESAL Barletta); Alberto Cappelli (Accademia dei Georgofili, Florence). The New Zealand Childhood Cancer Study was coordinated at the University of Otago, where the study team included JD Dockerty, GP Herbison (who helped prepare data for this pooled analysis), DCG Skegg and JM Elwood. The names of the interviewers, secretaries, research assistants, clinicians, pathologists, and cancer registry staff who contributed are listed in earlier publications from the NZ study. The UKCCS was conducted by 12 teams of investigators (ten clinical and epidemiological and two biological) based in university departments, research institutes, and the National Health Service in Scotland. Its work is coordinated by a management committee. Further information can be found on the web-site www.ukccs.org. COG: The E14 and E15 cohorts of the Children’s Oncology Group were identified by CCG (Children’s Cancer Group) principle and affiliate member institutions. Further information can be found on the Web site: http://www.curesearch.org/. The NCCLS thanks the families for their participation and the clinical investigators at the following collaborating hospitals for help in recruiting patients: University of California Davis Medical Center (Dr. J. Ducore), University of California San Francisco (Drs. M. Loh and K. Matthay), Children’s Hospital of Central California (Dr. V. Crouse), Lucile Packard Children’s Hospital (Dr. G. Dahl), Children’s Hospital Oakland (Dr. J. Feusner), Kaiser Permanente Roseville (former Sacramento; Drs. K. Jolly and V. Kiley), Kaiser Permanente Santa Clara (Drs. C. Russo, A. Wong, and D. Taggar), Kaiser Permanente San Francisco (Dr. K. Leung), and Kaiser Permanente Oakland (Drs. D. Kronish and S. Month). Finally, the NCCLS thanks the entire study staff and former University of California, Berkeley Survey Research Center for their effort and dedication. The French authors would like to thank all of the Société Française de lutte contre les Cancers de l’Enfant et de l’Adolescent (SFCE) principal investigators: André Baruchel (Hôpital Saint-Louis/Hôpital Robert Debré, Paris), Claire Berger (Centre Hospitalier Universitaire, Saint-Etienne), Christophe Bergeron (Centre Léon Bérard, Lyon), Jean-Louis Bernard (Hôpital La Timone, Marseille), Yves Bertrand (Hôpital Debrousse, Lyon), Pierre Bordigoni (Centre Hospitalier Universitaire, Nancy), Patrick Boutard (Centre Hospitalier Régional Universitaire, Caen), Gérard Couillault (Hôpital d’Enfants, Dijon), Christophe Piguet (Centre Hospitalier Régional Universitaire, Limoges), Anne-Sophie Defachelles (Centre Oscar Lambret, Lille), François Demeocq (Hôpital Hôtel-Dieu, Clermont-Ferrand), Alain Fischer (Hôpital des Enfants Malades, Paris), Virginie Gandemer (Centre Hospitalier Universitaire – Hôpital Sud, Rennes), Dominique Valteau-Couanet (Institut Gustave Roussy, Villejuif), Jean-Pierre Lamagnere (Centre Gatien de Clocheville, Tours), Françoise Lapierre (Centre Hospitalier Universitaire Jean Bernard, Poitiers), Guy Leverger (Hôpital Armand-Trousseau, Paris), Patrick Lutz (Hôpital de Hautepierre, Strasbourg), Geneviève Margueritte (Hôpital Arnaud de Villeneuve, Montpellier), Françoise Mechinaud (Hôpital Mère et Enfants, Nantes), Gérard Michel (Hôpital La Timone, Marseille), Frédéric Millot (Centre Hospitalier Universitaire Jean Bernard, Poitiers), Martine Münzer (American Memorial Hospital, Reims), Brigitte Nelken (Hôpital Jeanne de Flandre, Lille), Hélène Pacquement (Institut Curie, Paris), Brigitte Pautard (Centre Hospitalier Universitaire, Amiens), Stéphane Ducassou (Hôpital Pellegrin Tripode, Bordeaux), Alain Pierre-Kahn (Hôpital Enfants Malades, Paris), Emmanuel Plouvier (Centre Hospitalier Régional, Besançon), Xavier Rialland (Centre Hospitalier Universitaire, Angers), Alain Robert (Hôpital des Enfants, Toulouse), Hervé Rubie (Hôpital des Enfants, Toulouse), Stéphanie Haouy (Hôpital Arnaud de Villeneuve, Montpellier), Christine Soler (Fondation Lenval, Nice), and Jean-Pierre Vannier (Hôpital Charles Nicolle, Rouen). The Canada, Québec Study was conducted in the province over a 20-year period in all university-affiliated pediatric centers hospitals designated to diagnose and treat pediatric cancers, under the direction of Claire Infante-Rivard. Main support collaborators were Alexandre Cusson, Marcelle Petitclerc, and Denyse Hamer. We thank all families for their generous participation. The authors declare that they have no conflict of interest. The work reported in this paper by Helen Bailey was undertaken during the tenure of a Postdoctoral Fellowship from the International Agency for Research on Cancer, partially supported by the European Commission FP7 Marie Curie Actions—People—Co-funding of regional, national and international programmes (COFUND). The CLIC administration, annual meetings, and pooled analyses are partially supported by the National Cancer Institute, NCI, USA (grant R03CA132172), National Institute of Environmental Health Sciences, NIEHS, USA (grants P01 ES018172 and R13 ES021145-01), the Environmental Protection Agency, EPA, USEPA, USA (grant RD83451101), and the Children with Cancer, CwC, UK (Award No. 2010/097). Aus-ALL was supported by the Australian National Health and Medical Research Council (Grant ID 254539). The Canadian study was funded by The National Cancer Institute of Canada; Grant numbers: #014113, #010735-CERN #RFA0405; The Medical Research Council of Canada; Grant number: MOP 37951; The Fonds de la recherche en santé du Québec; Grant number: #981141; The Bureau of Chronic Disease Epidemiology, Canada; Health and Welfare Canada; The Leukemia Research Fund of Canada; and the National Health and Research Development Program, Ottawa. ADELE Grant sponsors: INSERM, the French Ministère de l’Environnement, the Association pour la Recherche contre le Cancer, the Fondation de France, the Fondation Jeanne Liot, the Fondation Weisbrem-Berenson, the Ligue Contre le Cancer du Val de Marne, the Ligue Nationale Contre le Cancer. ESCALE Grant sponsors: INSERM, the Fondation de France, the Association pour la Recherche sur le Cancer (ARC), the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), the AgenceFrançaise 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), the Cancéropôle Ile-de-France; The German study (GCCR) was supported by a grant from the Federal Ministry of the Environment, Nuclear Safety and Nature Preservation. NARECHEM, is supported in part by the National and Kapodistrian University, Athens, Greece. The SETIL study was financially supported by research grants received by AIRC (Italian Association on Research on Cancer), MIUR (Ministry for Instruction, University and Research), Ministry of Health, Ministry of Labour, Piedmont Region. The New Zealand Childhood Cancer Study was funded by the Health Research Council of 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. The Northern California Childhood Leukemia Study (NCCLS) is supported by the National Institutes of Health (NIH), USA (grants P01 ES018172, R01 ES09137, and P42-ES04705), Environmental Protection Agency (USEPA), USA (grant RD83451101), and the CHILDREN with CANCER (CwC), UK (former Children with Leukaemia), for data collection. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, USEPA, or the CwC. The United Kingdom Childhood Cancer Study (UKCCS) is sponsored and administered by Leukaemia and Lymphoma Research. The researchers are independent from the funders. COG: The E14 and E15 cohorts of the Children’s Oncology Group were funded by National Institutes of Health (NIH), USA (Grants R01CA049450 (E14) and R01CA048051 (E15)) and The Children’s Cancer Research Fund, Minneapolis, MN.
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