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BACKGROUND: Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide cancer rate, fewer than two cases would be expected. OBJECTIVES: In March 2001, the Centers for Disease Control and Prevention led federal, state, and local agencies in a cross-sectional, case-comparison study to determine if ongoing environmental exposures posed a health risk to residents and to compare levels of contaminants in environmental and biologic samples collected from participating families. METHODS: Surveys with more than 500 variables were administered to 205 people in 69 families. Blood, urine, and cheek cell samples were collected and analyzed for 139 chemicals, eight viral markers, and several genetic polymorphisms. Air, water, soil, and dust samples were collected from almost 80 homes to measure more than 200 chemicals. RESULTS: The scope of this cancer cluster investigation exceeded any previous study of pediatric leukemia. Nonetheless, no exposure consistent with leukemia risk was identified. Overall, tungsten and arsenic levels in urine and water samples were significantly higher than national comparison values+ADs- however, levels were similar among case and comparison groups. CONCLUSIONS: Although the cases in this cancer cluster may in fact have a common etiology, their small number and the length of time between diagnosis and our exposure assessment lessen the ability to find an association between leukemia and environmental exposures. Given the limitations of individual cancer cluster investigations, it may prove more efficient to pool laboratory and questionnaire data from similar leukemia clusters