Childhood acute lymphoblastic leukaemia and birthweight: insights from a pooled analysis of case-control data from Germany, the United Kingdom and the United States

TY - JOUR

T1 - Childhood acute lymphoblastic leukaemia and birthweight

T2 - insights from a pooled analysis of case-control data from Germany, the United Kingdom and the United States

AU - Roman, Eve

AU - Lightfoot, Tracy

AU - Smith, Alexandra G

AU - Forman, Michele R

AU - Linet, Martha S

AU - Robison, Les

AU - Simpson, Jill

AU - Kaatsch, Peter

AU - Grell, Kathrine

AU - Frederiksen, Kirsten

AU - Schüz, Joachim

N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.

PY - 2013/4

Y1 - 2013/4

N2 - Background: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes (<1500 and >4500 g), we pooled data from three of the largest childhood cancer case-control studies ever conducted. Methods: Birthweight and gestational age on 4075 children with ALL and 12,065 controls were collected during the course of three studies conducted in the USA, the UK and Germany in the 1990s. Information was obtained from mothers at interview, and the impact of bias was evaluated using the UK study which accessed birth registrations of participants and non-participants. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. Results: Children with ALL were, on average, heavier than controls at all gestations, the disparity being driven by a deficit of low-birthweight at all gestations and an excess of high-birthweight at ≥40 weeks. Overall, a 1.2 (95% CI 1.1-1.3) increase in ALL risk per kg increase in birthweight was observed; the ORs rising from 0.2 (0.1-0.7) at ≤1500 g through to 1.2 (0.9-1.6) at ≥4500 g; and 0.8 (0.7-0.9) <10th centile through to 1.3 (1.1-1.4) ≥90th centile. Conclusion: Our findings demonstrate the importance of looking across the full birthweight spectrum when examining associations with disease risk. The new observation of a deficit of very-low-birthweight cases at all gestations has aetiological and study design implications for future work examining not only the in utero origins of ALL, but also other childhood and adult cancers.

AB - Background: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes (<1500 and >4500 g), we pooled data from three of the largest childhood cancer case-control studies ever conducted. Methods: Birthweight and gestational age on 4075 children with ALL and 12,065 controls were collected during the course of three studies conducted in the USA, the UK and Germany in the 1990s. Information was obtained from mothers at interview, and the impact of bias was evaluated using the UK study which accessed birth registrations of participants and non-participants. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. Results: Children with ALL were, on average, heavier than controls at all gestations, the disparity being driven by a deficit of low-birthweight at all gestations and an excess of high-birthweight at ≥40 weeks. Overall, a 1.2 (95% CI 1.1-1.3) increase in ALL risk per kg increase in birthweight was observed; the ORs rising from 0.2 (0.1-0.7) at ≤1500 g through to 1.2 (0.9-1.6) at ≥4500 g; and 0.8 (0.7-0.9) <10th centile through to 1.3 (1.1-1.4) ≥90th centile. Conclusion: Our findings demonstrate the importance of looking across the full birthweight spectrum when examining associations with disease risk. The new observation of a deficit of very-low-birthweight cases at all gestations has aetiological and study design implications for future work examining not only the in utero origins of ALL, but also other childhood and adult cancers.

KW - Adolescent

KW - Birth Weight

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Confidence Intervals

KW - Female

KW - Germany

KW - Gestational Age

KW - Great Britain

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Logistic Models

KW - Male

KW - Odds Ratio

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Registries

KW - Risk Factors

KW - United States

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ejca.2012.11.017

DO - 10.1016/j.ejca.2012.11.017

M3 - Journal article

C2 - 23266048

SN - 0959-8049

VL - 49

SP - 1437

EP - 1447

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

IS - 6

ER -