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Eur J Epidemiol. 2018 Oct;33(10):965-976. doi: 10.1007/s10654-018-0402-z. Epub 2018 May 14.

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

Author information

1
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str, 11527, Athens, Greece. epetrid@med.uoa.gr.
2
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. epetrid@med.uoa.gr.
3
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str, 11527, Athens, Greece.
4
Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.
5
Unit of Survivorship, Childhood Cancer Survivorship Research Group, Danish Cancer Society Research Center, Copenhagen, Denmark.
6
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.
7
Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
8
Faculty of Social Sciences, University of Tampere, Tampere, Finland.
9
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
10
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
11
Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
12
Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, Heslington, York, UK.
13
School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
14
Dipartimento di Medicina Traslazionale, SCDU Epidemiologia del Tumori, Universitá del Piemonte Orientale, Novara, Italy.
15
Pediatric Hematology-Oncology Program, Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
16
Department of Epidemiology and Preventive Medicine, NLI-SSI Collaborative Research Center, National Liver Institute, Menoufia University, Cairo, Egypt.
17
Department of Pediatrics Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
18
Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica.
19
Department of Preventative and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
20
Danish Cancer Society Research Center, Copenhagen, Denmark.
21
Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
22
Biomedical Research Department, Armed Forces College of Medicine, Cairo, Egypt.
23
Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, QC, Canada.
24
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

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:

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

PMID:
29761423
PMCID:
PMC6384148
[Available on 2019-10-01]
DOI:
10.1007/s10654-018-0402-z

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