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

Eleni Th. Petridou, Marios K. Georgakis, Friederike Erdmann, Xiaomei Ma, Julia E. Heck, Anssi Auvinen, Beth A. Mueller, Logan G. Spector, Eve Roman, Catherine Metayer, Corrado Magnani, Maria S. Pombo-de-Oliveira, Sameera Ezzat, Michael E. Scheurer, Ana Maria Mora, John D. Dockerty, Johnni Hansen, Alice Y. Kang, Rong Wang, David R. DoodyEleanor Kane, Waffa M. Rashed, Nick Dessypris, Joachim Schüz, Claire Infante-Rivard, Alkistis Skalkidou

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40 Scopus citations


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 (OR CC 1.05, 95% CI 1.00–1.11; OR NCC 1.04, 95% CI 1.01–1.07). A similar positive association with advanced maternal age was observed only in the NCC results (OR CC 0.99, 95% CI 0.91–1.07, heterogeneity I 2 = 58%, p = 0.002; OR NCC 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.
Original languageEnglish (US)
Pages (from-to)965-976
Number of pages12
JournalEuropean Journal of Epidemiology
Issue number10
StatePublished - Oct 1 2018

Bibliographical note

Publisher Copyright:
© 2018, Springer Science+Business Media B.V., part of Springer Nature.


  • Acute lymphoblastic leukemia
  • Case–control
  • Childhood
  • Maternal age
  • Paternal age
  • Risk factors


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