This dissertation takes an integrated approach to understanding the causes of childhood cancer, examining early-life factors that may impact risk in population studies and mouse models.

The first study examined the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries. Subjects included 647 leukemia cases and 8,752 individuals sampled from the birth cohort from 1976-2004. Known risk factors for acute lymphoblastic leukemia were confirmed: male sex, high birth weight, and white race. An increased risk for acute myeloid leukemia and high birth weight was also found. Finally, low Apgar scores were associated with both leukemia subtypes. These results further solidify the link between leukemia and higher birth weight and raise the hypothesis that treatments following a low Apgar score, such as oxygen, could be involved in childhood leukemia etiology.

The second study examined whether cancer in the offspring of Radiologic Technologists (RTs) is increased with parental occupational radiation exposure. Standard survival analysis methods were used to calculate risk estimates. Prenatal and preconception radiation exposure were not significantly associated with childhood leukemia or solid tumors in the offspring. The risk of childhood lymphoma was increased with prenatal but not preconception exposure but did not appear to be related to radiation dose. Overall, this study does not support an increased risk of childhood cancer in the offspring of RTs associated with parental occupational radiation exposure and should largely be reassuring to those working in the medical radiation field.

The third study collected preliminary data using a mouse model to understand the effect of maternal folic acid intake in the perigestational period on leukemogenesis. Reproductive outcomes and B-lineage cell surface marker and gene expression were examined in pups of mothers randomized to folic acid varied diets. Results suggested no marked differences in the dams or the offspring with respect to litter size, sex ratio, weanling weight or the distribution of B-lineage cells. However, the maternal low and high folic acid diets were associated with significantly decreased pup survival. This study also suggests that maternal dietary folic acid may affect B-lineage gene expression in weanling pups.