Linabery, Amy Marie DeVries2011-02-162011-02-162010-03https://hdl.handle.net/11299/100405University of Minnesota. Ph.D. dissertation. March 2010. Major: Epidemiology. Advisor: Julie A. Ross. 1 computer file (PDF); xix, 287 pages, appendices A-K. Ill. (some col.)Little is known about the etiology of most pediatric hematologic malignancies, although there is evidence for prenatal initiation of leukemogenesis for many cases. The current body of research, a series of three complementary studies, evaluated the potential for unbiased measurement of prenatal exposures through retrieval of existing biospecimens and examined associations between pre- and postnatal exposures and pediatric/adolescent leukemia. The first study assessed the feasibility of retrospective collection of residual neonatal blood spots (NBS) for 947 childhood/adolescent leukemia and lymphoma cases from state newborn screening programs nationwide. Biological mothers were also asked to complete self-administered questionnaires regarding prenatal exposures, personal and family history of atopic disease, and selected demographic factors. Overall, 37% of families provided consent for NBS release and 41% of mothers completed questionnaires. Consenting cases were born in 39 states and 46 NBS were obtained from 5 states (CA, NY, MI, TX, and WA). NBS storage/release policies are rapidly evolving; requests are pending in states involved in litigation (MN), reviewing policies (NJ), and reviewing this study (MA). Currently, population-based NBS studies can be conducted in a limited number of states; fortunately, most of these have large populations to provide reasonable pediatric case and control groups. In the second study, the largest of its kind, the association between self-reported prenatal vitamin supplementation and infant leukemia was examined, since folic acid is postulated to play a preventative role in the pathogenesis of childhood leukemia, particularly among ALL cases. After adjustment for race/ethnicity and income, there was little evidence supporting associations between periconceptional vitamin use (OR = 0.89, 95% CI: 0.64-1.24), use after knowledge of pregnancy (OR = 0.78, 95% CI: 0.48-1.28), or use in all periods (OR = 0.84, 95% CI: 0.62-1.14) and infant leukemia. These results may be attributable to high rates of folic acid supplementation in the study population, including personal vitamin use and national folic acid fortification programs implemented in the U.S. and Canada early in the study period.</DISS_para> <DISS_para>Atopic disease is hypothesized to be protective for several malignancies. In the third study, meta-analysis was performed to summarize and quantify the risk of acute leukemia associated with atopic disease in children and adolescents and to identify sources of heterogeneity in the existing literature. Inverse associations were observed for ALL and atopy overall (OR = 0.69, 95% CI: 0.54-0.89)), and for asthma (OR = 0.79, 95% CI: 0.61-1.02), eczema (OR = 0.74, 95% CI: 0.58-0.96), and hay fever (OR = 0.55, 95% CI: 0.46-0.66) examined separately. ORs for ALL differed across strata of study design, exposure data source, and latency period, indicating these factors impact study results. Although these results should be interpreted cautiously given the modest number of studies, substantial heterogeneity, and potential exposure misclassification, they are useful in designing future research.en-USAtopyChildhood cancerEpidemiologic methodsMeta-analysisNeonatal blood spotsVitaminsEpidemiologyThesis or Dissertation