title: Risk for childhood leukemia associated with maternal and paternal age.
abstract: The role of reproductive factors, such as parental age, in the pathogenesis of childhood leukemias is being intensively examined; the results of individual studies are controversial. This meta-analysis aims to quantitatively synthesize the published data on the association between parental age and risk of two major distinct childhood leukemia types in the offspring. Eligible studies were identified and pooled relative risk (RR) estimates were calculated using random-effects models, separately for childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Subgroup analyses were performed by study design, geographical region, adjustment factors; sensitivity analyses and meta-regression analyses were also undertaken. 77 studies (69 case-control and eight cohort) were deemed eligible. Older maternal and paternal age were associated with increased risk for childhood ALL (pooled RR = 1.05, 95 % CI 1.01-1.10; pooled RR = 1.04, 95 % CI 1.00-1.08, per 5 year increments, respectively). The association between maternal age and risk of childhood AML showed a U-shaped pattern, with symmetrically associated increased risk in the oldest (pooled RR = 1.23, 95 % CI 1.06-1.43) and the youngest (pooled RR = 1.23, 95 % CI 1.07-1.40) extremes. Lastly, only younger fathers were at increased risk of having a child with AML (pooled RR = 1.28, 95 % CI 1.04-1.59). In conclusion, maternal and paternal age represents a meaningful risk factor for childhood leukemia, albeit of different effect size by leukemia subtype. Genetic and socio-economic factors may underlie the observed associations. Well-adjusted studies, scheduled by large consortia, are anticipated to satisfactorily address methodological issues, whereas the potential underlying genetic mechanisms should be elucidated by basic research studies.
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Sergentanis
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Thomopoulos
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.
authors.forename: Spyros P
authors.initials: SP
authors.lastname: Gialamas
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Karalexi
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.
authors.forename: Stylianos-Iason
authors.initials: SI
authors.lastname: Biniaris-Georgallis
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kontogeorgi
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Papathoma
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Tsilimidos
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Alkistis
authors.initials: A
authors.lastname: Skalkidou
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anastasia N
authors.initials: AN
authors.lastname: Iliadou
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National University of Athens, 75 M. Asias Str. Goudi, 115 27, Athens, Greece. epetrid@med.uoa.gr.
authors.forename: Eleni T
authors.initials: ET
authors.lastname: Petridou
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008423:Maternal Age; D010290:Parents; D010331:Paternal Age; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012959:Socioeconomic Factors
keywords: Childhood leukemia; Meta-analysis; Meta-regression; Parental age; Risk factor