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


METHODS
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 (SUOXgene), and aldehyde oxidase.


METHODS
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 SUOXgene locus and disease status in the presence of high tungsten and arsenic levels warrants further investigation.


CONCLUSIONS
Although analyses of community clusters of cancer have rarely identified causes, these findings have generated hypotheses to be tested in subsequent studies.
Steinberg
Karen K
KK
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. kks1@cdc.gov
Relling
Mary V
MV
Gallagher
Margaret L
ML
Greene
Christopher N
CN
Rubin
Carol S
CS
French
Deborah
D
Holmes
Adrianne K
AK
Carroll
William L
WL
Koontz
Deborah A
DA
Sampson
Eric J
EJ
Satten
Glen A
GA
D000293:Adolescent; D000328:Adult; D042931:Aldehyde Oxidase / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D009505:Nevada / Q000453:epidemiology; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*; D014968:Xanthine Dehydrogenase / Q000235:genetics
D014968:Xanthine Dehydrogenase; D042931:Aldehyde Oxidase; D050862:Oxidoreductases Acting on Sulfur Group Donors; C503599:SUOX protein, human