MATERNAL EXPOSURE TO POTENTIAL INHIBITORS OF DNA TOPOISOMERASE-II ANDINFANT LEUKEMIA (UNITED-STATES) - A REPORT FROM THE CHILDRENS CANCER GROUP

Nearly 80 percent of infant leukemias present with an abnormality invo lving the MLL gene at 11q23, Moreover, secondary acute myeloid leukemi as (AML) that occur as the result of chemotherapy agents, which are kn own to inhibit DNA topoisomerase II, often manifest the same MLL abnor malities, It has been hypothesized that de novo infant leukemias may o ccur as a result of maternal exposure to agents in diet and medication s that inhibit DNA topoisomerase II, Three epidemiologic studies of ch ildhood leukemia with similar methodologies were conducted in the Unit ed States and Canada over the past 10 years by the Children's Cancer G roup (CCG), Of the total 771 mothers of infants diagnosed at one year of age or less (< 12.5 months) who originally were interviewed (303 in fant cases and 468 matched controls) across the three studies, follow- up questionnaire data on maternal exposure to potential DNA topoisomer ase II inhibitors during pregnancy were available on 84 cases and 97 m atched controls in the US, For maternal diet, a composite variable was created that consisted of 10 foods identified a priori as containing DNA topoisomerase II inhibitors, There were no significant trends with increasing maternal consumption for either the overall group, or the acute lymphoblastic leukemia (ALL) stratum, However, within the AML st ratum, there was a statistically significant positive association (P t rend = 0.04) with increasing consumption of DNA topoisomerase II-inhib itor containing foods (odds ratio [OR] = 9.8, 95 percent confidence in terval [CI] = 1.1-84.8; OR = 10.2, CI = 1.1-96.4; for medium and high consumption, respectively), Other potential topoisomerase II inhibitor s were explored; no significant findings were found, Results of this p reliminary study, in combination with molecular data, should be used i n future investigations of childhood leukemia (particularly, infant) t o justify the incorporation of a detailed dietary history.