Maternal diet and infant leukemia: A role for DNA topoisomerase II inhibitors?

Leukemia in the first year of life is extremely rare worldwide. However, un like leukemias in older children, nearly 75% of infant leukemias demonstrat e a specific abnormality involving a gene, MLL on chromosome band 11q23. Mo lecular studies suggest strongly that these leukemias occur in utero, Treat ment-related acute myeloid leukemias (AML), associated with specific chemot herapeutic agents that inhibit DNA topoisomerase II (topo 2), also manifest identical abnormalities involving the MLL gene. This led us to speculate t hat maternal exposure during pregnancy to environmental agents that inhibit DNA topo 2 may be associated with the development of leukemia in infants. DNA topo 2 inhibitors have been found in specific fruits and vegetables, an d in soy, coffee, wine, tea and cocoa, as well as in certain pesticides, so lvents and medications. In a preliminary study, we reinterviewed mothers of infant cases and their matched controls who had participated previously in of 3 epidemiologic studies of childhood leukemia conducted by the Children 's Cancer Group over a IO-year period. We evaluated potential DNA topo 2 in hibitor exposure through maternal diet and medications. Of the 84 original matched sets who were reinterviewed, there was no positive association with increasing maternal consumption of DNA topo 2 inhibitor containing foods e ither for the overall group or for infants in the acute lymphoblastic leuke mia stratum. However, there was an approximately IO-fold higher risk of inf ant AML with increasing maternal consumption of DNA topo 2 inhibitor-contai ning foods. The assay to screen environmental agents that inhibit DNA topo 2 has been established and new inhibitors are being identified routinely. ( C) 1998 Wiley-Liss, Inc.