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Karen K. Steinberg,¹ Mary V. Relling,² Margaret L. Gallagher,¹ Christopher N. Greene,¹ Carol S. Rubin,³ Deborah French,² Adrianne K. Holmes,³ William L. Carroll,⁴ Deborah A. Koontz,¹ Eric J. Sampson,¹ and Glen A. Satten¹

¹Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ²Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; ³Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ⁴Hassenfeld Children's Center, New York University School of Medicine, New York, New York, USA

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.

Key words: arsenic, children, cluster, DDE, enzymes, genetics, leukemia, polymorphism, tungsten. Environ Health Perspect 115:158–164 (2007) . doi:10.1289/ehp.9025 available via http://dx.doi.org/ [Online 30 November 2006]

This article is part of the mini-monograph "Cancer Cluster Activities at the Centers for Disease Control and Prevention."

Address correspondence to K. Steinberg, Coordinating Center for Health Promotion, 2877 Brandywine Rd., Mailstop-K88, Koger Center, Williams Building, Room 3809, Chamblee, GA 30341 USA. Telephone: (770) 488-6067. Fax: (770) 488-6448. E-mail: kks1@cdc.gov

We express our appreciation for the guidance and advice of the Children's Oncology Group and K.V. Rajagopalan, Department of Biochemistry, Duke University.

This work was supported by National Cancer Institute grant CA 51001 and National Institutes of Health grant CA21765 ; by a Center of Excellence grant from the State of Tennessee ; and by American Lebanese Syrian Associated Charities.

The authors declare they have no competing financial interests.

Received 18 January 2006 ; accepted 19 July 2006.