Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium
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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.
KeywordsMaternal age Paternal age Acute lymphoblastic leukemia Childhood Risk factors Case–control
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.
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 was obtained from all individual participants included in the study.
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