This proposal is designed to identify etiologic associations between environmental exposures and childhood leukemia. The proposal expands an ongoing case control study of children ages 0 to 14 years that has been successfully implemented in 35 Northern and Central California counties. Notably, a high percentage of the subjects (about 40%) are children of Hispanic origin, which is unique in a study of childhood leukemia. Using a design that approximates population based ascertainment, the proposed study will expand the sample size (from 400 to 1148 newly diagnosed incident cases) and refine design and analytical procedures developed during the first five years of "Childhood Leukemia and Environmental Exposures" (R01 ES 09137, 1998-2003). Two matched control subjects for each case will be randomly selected from the statewide birth registry. Increased awareness of the molecular and cytogenetic diversity of leukemia within major subtypes (acute lymphoblastic leukemia and acute myeloid leukemia), and the significance of this diversity for clinical and epidemiologic research, underscore the need to uncover the etiologies of molecularly distinct subgroups of leukemia. We will use molecular-biologic techniques to differentiate leukemia subgroups and to identify the association of environment exposures with each molecular subgroup. For disease classification, biological specimens from case subjects will include pretreatment bone marrow and peripheral blood (collected at the time of diagnosis) and archived newborn blood specimens (collected at birth). To study genetic susceptibility, buccal cell specimens will be collected from cases, controls, and their biological mothers. To measure micronutrients and biomarkers of environmental chemical exposures, peripheral blood specimens will be collected from biological mothers of cases under age 7 and their matched controls. Data on a wide spectrum of environmental exposures (including parental occupational exposures, parental tobacco smoke, pesticides and other chemicals, maternal and child diet, and child immunological factors) will be collected through a detailed in-person interview with a biological parent. This comprehensive information on environmental exposures and genetic characteristics, in conjunction with improved disease classification and stratification by Hispanic status, will provide significant insights into the etiology of childhood leukemia.