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European Journal of Epidemiology

, Volume 33, Issue 10, pp 965–976 | Cite as

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

  • Eleni Th. PetridouEmail author
  • 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. Doody
  • Eleanor Kane
  • Waffa M. Rashed
  • Nick Dessypris
  • Joachim Schüz
  • Claire Infante-Rivard
  • Alkistis Skalkidou
CANCER

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.

Keywords

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

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

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

Supplementary material

10654_2018_402_MOESM1_ESM.docx (1 mb)
Supplementary material 1 (DOCX 1039 kb)

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Copyright information

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

Authors and Affiliations

  • Eleni Th. Petridou
    • 1
    • 2
    Email author
  • Marios K. Georgakis
    • 1
  • Friederike Erdmann
    • 3
    • 4
  • Xiaomei Ma
    • 5
  • Julia E. Heck
    • 6
  • Anssi Auvinen
    • 7
  • Beth A. Mueller
    • 8
    • 9
  • Logan G. Spector
    • 10
  • Eve Roman
    • 11
  • Catherine Metayer
    • 12
  • Corrado Magnani
    • 13
  • Maria S. Pombo-de-Oliveira
    • 14
  • Sameera Ezzat
    • 15
  • Michael E. Scheurer
    • 16
  • Ana Maria Mora
    • 17
  • John D. Dockerty
    • 18
  • Johnni Hansen
    • 19
  • Alice Y. Kang
    • 12
  • Rong Wang
    • 5
  • David R. Doody
    • 8
  • Eleanor Kane
    • 11
  • Waffa M. Rashed
    • 20
    • 21
  • Nick Dessypris
    • 1
  • Joachim Schüz
    • 3
  • Claire Infante-Rivard
    • 22
  • Alkistis Skalkidou
    • 23
  1. 1.Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.Clinical Epidemiology Unit, Department of MedicineKarolinska InstituteStockholmSweden
  3. 3.Section of Environment and RadiationInternational Agency for Research on CancerLyonFrance
  4. 4.Unit of Survivorship, Childhood Cancer Survivorship Research GroupDanish Cancer Society Research CenterCopenhagenDenmark
  5. 5.Department of Chronic Disease Epidemiology, Yale School of Public Health, Cancer Prevention and Control, Yale Comprehensive Cancer CenterYale School of MedicineNew HavenUSA
  6. 6.Department of Epidemiology, School of Public HealthUniversity of California, Los AngelesLos AngelesUSA
  7. 7.Faculty of Social SciencesUniversity of TampereTampereFinland
  8. 8.Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  9. 9.Department of Epidemiology, School of Public HealthUniversity of WashingtonSeattleUSA
  10. 10.Division of Epidemiology and Clinical Research, Department of PediatricsUniversity of MinnesotaMinneapolisUSA
  11. 11.Epidemiology and Cancer Statistics Group, Department of Health SciencesUniversity of YorkHeslingtonUK
  12. 12.School of Public HealthUniversity of California, BerkeleyBerkeleyUSA
  13. 13.Dipartimento di Medicina Traslazionale, SCDU Epidemiologia del TumoriUniversitá del Piemonte OrientaleNovaraItaly
  14. 14.Pediatric Hematology-Oncology ProgramInstituto Nacional de CancerRio de JaneiroBrazil
  15. 15.Department of Epidemiology and Preventive Medicine, NLI-SSI Collaborative Research Center, National Liver InstituteMenoufia UniversityCairoEgypt
  16. 16.Department of Pediatrics Texas Children’s Cancer CenterBaylor College of MedicineHoustonUSA
  17. 17.Central American Institute for Studies on Toxic Substances (IRET)Universidad NacionalHerediaCosta Rica
  18. 18.Department of Preventative and Social Medicine, Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand
  19. 19.Danish Cancer Society Research CenterCopenhagenDenmark
  20. 20.Research DepartmentChildren’s Cancer Hospital EgyptCairoEgypt
  21. 21.Biomedical Research DepartmentArmed Forces College of MedicineCairoEgypt
  22. 22.Department of Epidemiology, Biostatistics and Occupational Health, Faculty of MedicineMcGill UniversityMontrealCanada
  23. 23.Department of Women’s and Children’s HealthUppsala UniversityUppsalaSweden

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