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Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium

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Abstract

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0–14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case–control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case–control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968–2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1.05, 95% CI 1.00–1.11; ORNCC 1.04, 95% CI 1.01–1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91–1.07, heterogeneity I2 = 58%, p = 0.002; ORNCC 1.05, 95% CI 1.01–1.08). The positive association between parental age and risk of ALL was most marked among children aged 1–5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.

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Acknowledgements

The CLIC studies thank the families for their consent and participation, the study staff, interviewers and pediatric oncologists for their support as well as Dr Constantinos Mihas and Dr Antonis Analytis for their contributions to statistical analyses. Acknowledgements by study site are shown in the Supplementary materials.

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Authors and Affiliations

  1. Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str, 11527, Athens, Greece

    Eleni Th. Petridou, Marios K. Georgakis & Nick Dessypris

  2. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

    Eleni Th. Petridou

  3. Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France

    Friederike Erdmann & Joachim Schüz

  4. Unit of Survivorship, Childhood Cancer Survivorship Research Group, Danish Cancer Society Research Center, Copenhagen, Denmark

    Friederike Erdmann

  5. Department of Chronic Disease Epidemiology, Yale School of Public Health, Cancer Prevention and Control, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA

    Xiaomei Ma & Rong Wang

  6. Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA

    Julia E. Heck

  7. Faculty of Social Sciences, University of Tampere, Tampere, Finland

    Anssi Auvinen

  8. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Beth A. Mueller & David R. Doody

  9. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA

    Beth A. Mueller

  10. Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Logan G. Spector

  11. Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, Heslington, York, UK

    Eve Roman & Eleanor Kane

  12. School of Public Health, University of California, Berkeley, Berkeley, CA, USA

    Catherine Metayer & Alice Y. Kang

  13. Dipartimento di Medicina Traslazionale, SCDU Epidemiologia del Tumori, Universitá del Piemonte Orientale, Novara, Italy

    Corrado Magnani

  14. Pediatric Hematology-Oncology Program, Instituto Nacional de Cancer, Rio de Janeiro, Brazil

    Maria S. Pombo-de-Oliveira

  15. Department of Epidemiology and Preventive Medicine, NLI-SSI Collaborative Research Center, National Liver Institute, Menoufia University, Cairo, Egypt

    Sameera Ezzat

  16. Department of Pediatrics Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Michael E. Scheurer

  17. Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica

    Ana Maria Mora

  18. Department of Preventative and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

    John D. Dockerty

  19. Danish Cancer Society Research Center, Copenhagen, Denmark

    Johnni Hansen

  20. Research Department, Children’s Cancer Hospital Egypt, Cairo, Egypt

    Waffa M. Rashed

  21. Biomedical Research Department, Armed Forces College of Medicine, Cairo, Egypt

    Waffa M. Rashed

  22. Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, QC, Canada

    Claire Infante-Rivard

  23. Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

    Alkistis Skalkidou

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  1. Eleni Th. Petridou
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  2. Marios K. Georgakis
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Correspondence to Eleni Th. Petridou.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

Additional information

Core Writing Group: Eleni Th. Petridou, Marios K. Georgakis, Friederike Erdmann, Logan G. Spector, Eve Roman, Sameera Ezzat, Ana Maria Mora, Nick Dessypris, Joachim Schüz, Claire Infante-Rivard and Alkistis Skalkidou.

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Petridou, E.T., Georgakis, M.K., Erdmann, F. et al. Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium. Eur J Epidemiol 33, 965–976 (2018). https://doi.org/10.1007/s10654-018-0402-z

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