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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