Several exposures and experiences have been associated with
younger age childhood leukemias, typically in children diagnosed
less than 2 years of age. These include maternal alcohol
consumption during pregnancy, maternal pesticide and solvent
exposure during pregnancy, and infant birthweight in excess of
4000 grams. However, a diagnosis of less than 2 years of age is
an inadequate characterization of infant leukemia. There are
marked differences in clinical behavior and frequency of a
specific genetic abnormality in cases diagnosed less than 1 year
of age compared to cases diagnosed at older ages. Approximately
60 percent of infants with acute myeloid leukemia (AML) and 80
percent of infants with acute lymphoblastic leukemia (ALL) have a
molecular abnormality in their leukemia cells involving the gene,
MLL, at chromosome band 11q23; the frequency of this abnormality
drops precipitously after 1 year of age. There is substantial
evidence that these MLL abnormalities occur during pregnancy.
Thus, infants with leukemia may be a highly informative subgroup
for the identification of possible environmental exposures in
utero that act as initiators. This case-control study will
include infants with ALL and AML and randomly selected,
individually-matched controls. This study is designed to explore
the following in this unique patient population (1) maternal
exposure to DNA topoisomerase II inhibitors during pregnancy is
associated with infant AML that manifests MLL abnormalities; (2)
mothers of infant cases are more likely to have exposures to
pesticides and solvents during pregnancy; (3) in utero exposure
to alcohol is associated with an increased risk of infant AML;
(4) mothers of female cases are more likely to have a
reproductive history that included fetal loss prior to the
pregnancy of the index child; (5) infant cases, particularly ALL,
will weigh more than infant controls; and (6) there will be a
higher frequency of MLL abnormalities among female infants with
leukemia compared with male infants with leukemia. This study
will utilize the unique resources available through the
Children's Cancer Group, and include ascertainment of cases over
a six-year period (Jan 1, 1996-Dec 31, 2001). Included in this
study will be the integration of molecular data documenting the
presence or absence of an MLL abnormality. The overall sample
size includes 250 matched sets (2 controls per case), which will
provide sufficient statistical power to address the hypothesis
being investigated.
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- The DCCPS Team.