The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C)
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The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C). / Paltiel, Ora; Lemeshow, Stanley; Phillips, Gary S.; Tikellis, Gabriella; Linet, Martha S.; Ponsonby, Anne Louise; Magnus, Per; Håberg, Siri E.; Olsen, Sjurdur F.; Granström, Charlotta; Klebanoff, Mark; Golding, Jean; Herceg, Zdenko; Ghantous, Akram; Hirst, Jane Elizabeth; Borkhardt, Arndt; Ward, Mary H.; Holst Søegaard, Signe; Dwyer, Terence.
In: International Journal of Cancer, Vol. 144, No. 1, 2019, p. 26-33.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C)
AU - Paltiel, Ora
AU - Lemeshow, Stanley
AU - Phillips, Gary S.
AU - Tikellis, Gabriella
AU - Linet, Martha S.
AU - Ponsonby, Anne Louise
AU - Magnus, Per
AU - Håberg, Siri E.
AU - Olsen, Sjurdur F.
AU - Granström, Charlotta
AU - Klebanoff, Mark
AU - Golding, Jean
AU - Herceg, Zdenko
AU - Ghantous, Akram
AU - Hirst, Jane Elizabeth
AU - Borkhardt, Arndt
AU - Ward, Mary H.
AU - Holst Søegaard, Signe
AU - Dwyer, Terence
N1 - Publisher Copyright: © 2018 UICC
PY - 2019
Y1 - 2019
N2 - The “delayed infection hypothesis” states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 10 6 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77–0.99) and 0.85: (0.73–0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58–1.05 and 0.73: 0.52–1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06–0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.
AB - The “delayed infection hypothesis” states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 10 6 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77–0.99) and 0.85: (0.73–0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58–1.05 and 0.73: 0.52–1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06–0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.
KW - acute lymphoblastic leukemia
KW - birth order
KW - birth weight
KW - childhood leukemia
KW - cohort studies
KW - paternal age
U2 - 10.1002/ijc.31635
DO - 10.1002/ijc.31635
M3 - Journal article
C2 - 30098208
AN - SCOPUS:85055737828
VL - 144
SP - 26
EP - 33
JO - Acta - Unio Internationalis Contra Cancrum
JF - Acta - Unio Internationalis Contra Cancrum
SN - 0898-6924
IS - 1
ER -
ID: 306542688