Aspects of the natural history of childhood leukaemia by historyman



Aspects of the natural history of
childhood leukaemia
Lisa Lyngsie Hjalgrim

This PhD dissertation was accepted by the Faculty of Health Sciences of the
University of Copenhagen, and defended on March 19, 2004.
Official opponents: Mikael Rørth, Jørgen H. Olsen, and Steen Rosthøj.
Supervisors: Kjeld Schmiegelow and Mads Melbye.
Correspondence: Lisa Lyngsie Hjalgrim, Søvangs Alle 12, DK-3500 Værløse.

Dan Med Bull 2004;51:223.

The studies included in this PhD dissertation were carried out at the
Department of Epidemiology Research, Statens Serum Institut, and
focus on characterising the occurrence of childhood leukaemia, tim-
ing of critical genetic events involved in childhood leukaemia devel-
opment, and the identification of pregnancy-related risk factors for
childhood leukaemia with particular emphasis on acute lympho-
blastic leukaemia (ALL). Using a unique population-based register
of all cases of leukaemia diagnosed in children in the Nordic coun-
tries since 1982 (Nordic childhood leukaemia database), we demon-
strated stable incidence rates of childhood leukaemia over the last 20
years. This observation suggests that no marked changes in expos-
ures to risk factors for childhood leukaemia have occurred during
this period. In a molecular-biological analysis of neonatal blood
samples, we found evidence that the development of t(12;21) B-pre-
cursor ALL may be initiated in utero. Together with other informa-
tion this observation is in accordance with the hypothesis that ALL
in childhood develops as a multiple step process involving both pre-
and postnatal genetic events. In two studies, we observed a statistic-
ally significant correlation between birth weight and ALL risk, ap-
parent for all ALL subtypes and diagnostic age groups. Using infor-
mation on families, we found that children with leukaemia do not
weigh more than their siblings at birth, but that siblings of children
with leukaemia weigh more at birth than children in general. These
findings are consistent with the hypothesis that increasing birth
weight modifies the leukaemia risk through proliferative stress
and/or by correlating with number of cells at risk of critical genetic
aberrations. Our study also showed a reduced risk of ALL with in-
creasing birth order. This association is in accordance with the so-
called “delayed infection hypothesis”, proposing that postponed ex-
posure to common infections may increase the risk of childhood
ALL. Future studies should aim at determining the frequency of the
most common genetic traits associated with leukaemia in childhood
in healthy newborns, preferably in different populations, and at
identifying risk factors for these, possibly initiating, genetic aberra-

DANISH MEDICAL BULLETIN VOL.   51   NO.   27/MAY 2004                         223

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