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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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 (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)
JournalEuropean Journal of Epidemiology
Volume33
Issue number10
DOIs
StatePublished - 2018

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Paternal Age
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Maternal Age
Leukemia
Parents
Odds Ratio
Meta-Analysis
Health
Cytogenetics
Registries
Mothers
Interviews
Population

Bibliographical note

<p>--BEGIN ADMIN-EDITABLE FIELDS--<br/>NSFID:<br/>PMCID:<br/>DEGREE:<br/>ADVISOR:<br/>--END ADMIN-EDITABLE FIELDS DO NOT EDIT BELOW--</p>

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Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium. / Petridou, Eleni Th.; Georgakis, Marios K.; Erdmann, Friederike; Ma, Xiaomei; Heck, Julia E.; Auvinen, Anssi; Mueller, Beth A.; Spector, Logan G.; Roman, Eve; Metayer, Catherine; Magnani, Corrado; Pombo-de-Oliveira, Maria S.; Ezzat, Sameera; Scheurer, Michael E.; Mora, Ana Maria; Dockerty, John D.; Hansen, Johnni; Kang, Alice Y.; Wang, Rong; Doody, David R.; Kane, Eleanor; Rashed, Waffa M.; Dessypris, Nick; Schüz, Joachim; Infante-Rivard, Claire; Skalkidou, Alkistis.

In: European Journal of Epidemiology, Vol. 33, No. 10, 2018.

Research output: Contribution to journalArticle

Petridou, ET, Georgakis, MK, Erdmann, F, Ma, X, Heck, JE, Auvinen, A, Mueller, BA, Spector, LG, Roman, E, Metayer, C, Magnani, C, Pombo-de-Oliveira, MS, Ezzat, S, Scheurer, ME, Mora, AM, Dockerty, JD, Hansen, J, Kang, AY, Wang, R, Doody, DR, Kane, E, Rashed, WM, Dessypris, N, Schüz, J, Infante-Rivard, C & Skalkidou, A 2018, 'Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium', European Journal of Epidemiology, vol. 33, no. 10. https://doi.org/10.1007/s10654-018-0402-z
Petridou, Eleni Th. ; Georgakis, Marios K. ; Erdmann, Friederike ; Ma, Xiaomei ; Heck, Julia E. ; Auvinen, Anssi ; Mueller, Beth A. ; Spector, Logan G. ; Roman, Eve ; Metayer, Catherine ; Magnani, Corrado ; Pombo-de-Oliveira, Maria S. ; Ezzat, Sameera ; Scheurer, Michael E. ; Mora, Ana Maria ; Dockerty, John D. ; Hansen, Johnni ; Kang, Alice Y. ; Wang, Rong ; Doody, David R. ; Kane, Eleanor ; Rashed, Waffa M. ; Dessypris, Nick ; Schüz, Joachim ; Infante-Rivard, Claire ; Skalkidou, Alkistis. / Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium. In: European Journal of Epidemiology. 2018 ; Vol. 33, No. 10.
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AU - Petridou, Eleni Th.

AU - Georgakis, Marios K.

AU - Erdmann, Friederike

AU - Ma, Xiaomei

AU - Heck, Julia E.

AU - Auvinen, Anssi

AU - Mueller, Beth A.

AU - Spector, Logan G.

AU - Roman, Eve

AU - Metayer, Catherine

AU - Magnani, Corrado

AU - Pombo-de-Oliveira, Maria S.

AU - Ezzat, Sameera

AU - Scheurer, Michael E.

AU - Mora, Ana Maria

AU - Dockerty, John D.

AU - Hansen, Johnni

AU - Kang, Alice Y.

AU - Wang, Rong

AU - Doody, David R.

AU - Kane, Eleanor

AU - Rashed, Waffa M.

AU - Dessypris, Nick

AU - Schüz, Joachim

AU - Infante-Rivard, Claire

AU - Skalkidou, Alkistis

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N2 - 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.

AB - 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.

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JO - European Journal of Epidemiology

JF - European Journal of Epidemiology

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