Superfund Research Program

Biomarker Laboratory Core

Project Leader: Nina T. Holland
Grant Number: P42ES004705
Funding Period: 2000 - 2006

Project-Specific Links

Final Progress Reports

Year:   2005 

Investigating the role of environmental and genetic factors in childhood leukemia requires a systematic means of storing, processing and analyzing biospecimens from affected children and their mothers. Core B provides this vital link to the environmental and genetic epidemiological efforts in the program. During this year Core B provided uniform processing and DNA extraction from cheek cell specimens from 422 children with leukemia and their mothers. These samples are mailed in to the laboratory from the field by interviewers and parents. Careful archiving of the specimens and distribution of DNA to the appropriate labs for analysis is the first goal of the Core and this has now been achieved for some 3044 study participants over the entire study. A second function of Core B is to carry out genotyping of cheek samples for genes that are believed to modify the effects of environmental toxins. This year analyses were conducted on 344 research subjects involving 8 different gene variants involving enzymes that modify the metabolism of environmental agents. Finally, the challenge for future research is to provide methods to examine many thousands of genes that are being identified as potentially important in childhood leukemia and to make full use of the dramatic advances of the human genome and HapMap projects. To this end the core has developed and tested several methods for expanding the limited amounts of DNA obtained by cheek cell sampling for extensive future analyses. Their pilot studies indicate that several procedures are viable given appropriate quality controls are employed in the process of whole genome amplification. Finally, Core B has published an important set of findings on the cancerous RAS mutations in leukemic cells that they found to be associated with smoking among the fathers of children with leukemia and within specific subtypes of the diseases and smoking by fathers prior to conception of the child. These results provide additional support that the researchers can identify preventable causes of childhood leukemia and the value of molecular analyses in environmental epidemiologic studies. Core B provides a key link between the environmental scientists and genetic and epidemiologic researchers by providing a high quality repository of specimens and genetic analyses that can be used to explore potential causes of childhood leukemia.