Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada

• Authors: Karen K. Steinberg, Centers for Disease Control and Prevention; Mary V. Relling, St. Jude Children’s Research Hospital; Margaret L. Gallagher, Centers for Disease Control and Prevention; Christopher N. Greene, Centers for Disease Control and Prevention; Carol S. Rubin, Centers for Disease Control and Prevention; Deborah French, St. Jude Children’s Research Hospital; Adrianne K. Holmes, Centers for Disease Control and Prevention; William L. Carroll, New York University; Deborah A. Koontz, Centers for Disease Control and Prevention; Eric J. Sampson, Centers for Disease Control and Prevention; Glen Satten, Emory University
• Journal Title: Environmental Health Perspectives
• Volume: Volume 115, Number 1
• Publisher: National Institute of Environmental Health Sciences (NIEHS) | 2007-01-01, Pages 158-164
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1289/ehp.9025
• Subjects: Health Sciences, Public Health; Biology, Ecology; Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Environmental Sciences; Public, Environmental & Occupational Health; Toxicology; Environmental Sciences & Ecology; arsenic; children; cluster; DDE; enzymes; genetics; leukemia; polymorphism; tungsten; CHILDHOOD LEUKEMIA; SULFITE OXIDASE; TUNGSTEN; POLYMORPHISMS; MECHANISMS; SUSCEPTIBILITY; MUTAGENESIS; MOLYBDENUM; DEFICIENCY; INFERENCE

Abstract

Objective: In a study to identify exposures associated with 15 cases of childhood leukemia, we found levels of tungsten, arsenic, and dichlorodiphenyldichloroethylene in participants to be higher than mean values reported in the National Report on Human Exposure to Environmental Chemicals. Because case and comparison families had similar levels of these contaminants, we conducted genetic studies to identify gene polymorphisms that might have made case children more susceptible than comparison children to effects of the exposures. Design: We compared case with comparison children to determine whether differences existed in the frequency of polymorphic genes, including genes that code for enzymes in the folate and purine pathways. We also included discovery of polymorphic forms of genes that code for enzymes that are inhibited by tungsten: xanthine dehydrogenase, sulfite oxidase (SUOX gene), and aldehyde oxidase. Participants: Eleven case children were age- and sex-matched with 42 community comparison children for genetic analyses. Twenty parents of case children also contributed to the analyses. Results: One bilalleleic gene locus in SUOX was significantly associated with either case or comparison status, depending on which alleles the child carried (without adjusting for multiple comparisons). Conclusions: Although genetic studies did not provide evidence that a common agent or genetic susceptibility factor caused the leukemias, the association between a SUOX gene locus and disease status in the presence of high tungsten and arsenic levels warrants further investigation. Relevance: Although analyses of community clusters of cancer have rarely identified causes, these findings have generated hypotheses to be tested in subsequent studies.