Parental Exposure to Specific Chemicals May Lead to Mutations in Children Leading to Acute Lymphoblastic Leukemia

Leslie L. Robison, Ph.D.
Department of Pediatrics
University of Minnesota
R01ES07819

Background: The ras proto-oncogene family of genes has three members: H-ras, K-ras, and N-ras. The protein products of these genes share much similarity between organisms and they transmit proliferative signals from cytokines and growth factors to the nucleus. Ras proto-oncogene mutations have been implicated in the development of many malignancies including pancreatic and breast cancers. However, little data exists associating ras mutations with parental exposures and risk of childhood leukemia.

Advance: To investigate the connection of chemical exposures in parents and their childrens' risk of developing acute lymphoblastic leukemia (ALL), this NIEHS-supported study employed an epidemiologic approach using data from a large case-control study of childhood ALL conducted by the Children's Oncology Group in Southern California. DNA samples from the children in the study were examined for ras mutations. A total of 127 out of 837 ALL cases exhibited ras mutations in the K- or N-ras genes. A number of chemical exposures were associated with significantly increased risks for development of ALL in children. Parental use of "mind-altering drugs," such as marijuana, LSD, and cocaine was associated with increased risk for ALL (three-fold higher risk for maternal use and two-fold higher risk for paternal use). Maternal exposure to solvents and plastics during pregnancy raised the risk about three-fold and seven-fold respectively and maternal exposure to plastics after pregnancy was associated with eight times higher risk. Other exposures, such as to oil and coal products, were also associated with increased risks of ALL.

Implication: In previous studies, parental occupational exposure to hydrocarbons, such as chlorinated solvents, benzene, and paints, has been linked to elevated childhood leukemia risk. The present study has extended these findings to include drugs of abuse and additional chemical exposures and to link them to ras mutations. The study's authors conclude that parental exposures to "hydrocarbons and mind-altering drugs, chemicals that have been previously suggested to increase the risk of childhood leukemia, [are] related to specific ras mutations in childhood ALL."

Citation: Shu XO, Perentesis JP, Wen W, Buckley JD, Boyle E, Ross JA, Robison LL; Children's Oncology Group. Parental exposure to medications and hydrocarbons and ras mutations in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group. Cancer Epidemiol Biomarkers Prev. 2004 Jul;13(7):1230-5.