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)

Ora Paltiel, Stanley Lemeshow, Gary S. Phillips, Gabriella Tikellis, Martha S. Linet, Anne Louise Ponsonby, Per Magnus, Siri E. Håberg, Sjurdur F. Olsen, Charlotta Granström, Mark Klebanoff, Jean Golding, Zdenko Herceg, Akram Ghantous, Jane Elizabeth Hirst, Arndt Borkhardt, Mary H. Ward, Signe Holst Søegaard, Terence Dwyer

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalInternational Journal of Cancer
Volume144
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Keywords

  • acute lymphoblastic leukemia
  • birth order
  • birth weight
  • childhood leukemia
  • cohort studies
  • paternal age

Cite this

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. / 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). In: International Journal of Cancer. 2019 ; Vol. 144, No. 1. pp. 26-33.
@article{3697a725068f457da58ed3a08f98aeec,
title = "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)",
abstract = "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.",
keywords = "acute lymphoblastic leukemia, birth order, birth weight, childhood leukemia, cohort studies, paternal age",
author = "Ora Paltiel and Stanley Lemeshow and Phillips, {Gary S.} and Gabriella Tikellis and Linet, {Martha S.} and Ponsonby, {Anne Louise} and Per Magnus and H{\aa}berg, {Siri E.} and Olsen, {Sjurdur F.} and Charlotta Granstr{\"o}m and Mark Klebanoff and Jean Golding and Zdenko Herceg and Akram Ghantous and Hirst, {Jane Elizabeth} and Arndt Borkhardt and Ward, {Mary H.} and {Holst S{\o}egaard}, Signe and Terence Dwyer",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ijc.31635",
language = "English",
volume = "144",
pages = "26--33",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Blackwell",
number = "1",

}

Paltiel, O, Lemeshow, S, Phillips, GS, Tikellis, G, Linet, MS, Ponsonby, AL, Magnus, P, Håberg, SE, Olsen, SF, Granström, C, Klebanoff, M, Golding, J, Herceg, Z, Ghantous, A, Hirst, JE, Borkhardt, A, Ward, MH, Holst Søegaard, S & Dwyer, T 2019, '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)', International Journal of Cancer, vol. 144, no. 1, pp. 26-33. https://doi.org/10.1002/ijc.31635

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, 01.01.2019, p. 26-33.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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

PY - 2019/1/1

Y1 - 2019/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=85055737828&partnerID=8YFLogxK

U2 - 10.1002/ijc.31635

DO - 10.1002/ijc.31635

M3 - Article

C2 - 30098208

AN - SCOPUS:85055737828

VL - 144

SP - 26

EP - 33

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 1

ER -