Superfund Research Program

Biomarkers of Chemical Exposure and Leukemia Risk

Project Leader: Martyn T. Smith
Co-Investigator: Patricia A. Buffler
Grant Number: P42ES004705
Funding Period: 1995 - 2011

Project-Specific Links

Final Progress Reports

Year:   2010  2005 

The case-control study of childhood leukemia in Northern and Central California (NCCLS) has completed a full year of participation by its nine collaborating hospitals. Dr. Buffler and her research team have completed a total of 816 interviews on eligible and consenting childhood leukemia cases since 1995 up to October 2005. Control selection, personal interview, and follow-back (Tier 2) home visits continue to be efficiently managed by the Survey Research Center at UC Berkeley. Collection of biological specimens is progressing well. A total of 92 subjects have completed the Tier 2 visits over the last year (leading to a total of 428 subjects), which include validation of self-reported use of chemicals in the home and collection of dust and air samples. Laboratory analyses of the home samples and planning for statistical analyses related to methodological studies and risk assessment is underway.

In 2005, the NCCLS has published a total of 10 peer-reviewed journal articles, and an additional 4 manuscripts have been submitted for review. In the researchers’ evaluation of the role of infectious exposures in childhood leukemia etiology (294 cases and 376 controls), daycare attendance measured by child-hours was associated with a significantly reduced risk of acute lymphoblastic leukemia (ALL) in non-Hispanic White children (OR=0.42). In addition, self-reported ear infection during infancy was associated with a significantly reduced risk of common ALL (OR=0.32). These associations were not observed in Hispanic children which suggests an important ethnic difference. In the researchers’ evaluation of the effect of vaccinations (323 cases and 409 controls), compared to children who received two or fewer does of Haemophilus influenzae b (Hib) vaccine, those who received three or more doses had a significantly reduced risk of childhood leukemia (OR=0.55).

Project investigators examined the relationship between maternal illness and drug use surrounding the pregnancy and risk of childhood leukemia (365 case-control sets). History of maternal flu/pneumonia before, during, or after pregnancy was associated with a significant increased risk of ALL in the offspring (OR=1.89). Other maternal influences on risk of leukemia in the offspring include a reduced risk associated with iron supplement use (OR=0.67) and an increased risk associated with recreational drug use before, during, or after pregnancy (OR=1.74). In the investigators’ evaluation of reproductive history and birth characteristics (313 ALL, 53 AML cases and 460 controls), an increased risk of acute myeloid leukemia (AML) was associated with a history of miscarriage (OR=2.94). Neither birth weight, birth order, nor parental ages appeared to be an important risk factor of ALL or AML.

The researchers characterized the cytogenetics of 543 childhood leukemia patients enrolled in the NCCLS and compared the cytogenetic profiles between Hispanics and non-Hispanic Whites. The ploidy levels most frequently observed among ALL patients were high hyperdiploidy (51-67 chromosomes) and pseudodiploidy. Among B lineage ALL patients, the percentage of TEL-AML1 translocations was significantly lower in Hispanics (13%) than in non-Hispanic Whites (24%). The researchers are also currently investigating the interplay between genetic polymorphisms and environment exposures on childhood leukemia risk including folate metabolism genes and folate intake, chemical metabolism genes and parental smoking and membrane transporter genes and pesticides.