title: Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion.
abstract: Infant acute leukemia (IAL) frequently involves breakage and recombination of the MLL gene with one of several potential partner genes. These gene fusions arise in utero and are similar to those found in leukemias secondary to chemotherapy with inhibitors of topoisomerase II (topo-II). This has led to the hypothesis that in utero exposures to chemicals may cause IAL via an effect on topo-II. We report a pilot case-control study of IAL across different countries and ethnic groups. Cases (n = 136) were population-based in most centers. Controls (n = 266) were selected from inpatients and outpatients at hospitals serving the same populations. MLL rearrangement status was derived by Southern blot analysis, and maternal exposure data were obtained by interviews using a structured questionnaire. Apart from the use of cigarettes and alcohol, very few mothers reported exposure to known topo-II inhibitors. Significant case-control differences were apparent for ingestion of several groups of drugs, including herbal medicines and drugs classified as "DNA-damaging," and for exposure to pesticides with the last two being largely attributable, respectively, to one nonsteroidal anti-inflammatory drug, dipyrone, and mosquitocidals (including Baygon). Elevated odds ratios were observed for MLL+ve (but not MLL-ve) leukemias (2.31 for DNA-damaging drugs, P = 0.03; 5.84 for dipyrone, P = 0.001; and 9.68 for mosquitocidals, P = 0.003). Although it is unclear at present whether these particular exposures operate via an effect on topo-II, the data suggest that specific chemical exposures of the fetus during pregnancy may cause MLL gene fusions. Given the widespread use of dipyrone, Baygon, and other carbamate-based insecticides in certain settings, confirmation of these apparent associations is urgently required.
authors: Department of Public Health Science, University of Edinburgh, United Kingdom.
authors: F E
authors: FE
authors: Alexander
authors: S L
authors: SL
authors: Patheal
authors: A
authors: A
authors: Biondi
authors: S
authors: S
authors: Brandalise
authors: M E
authors: ME
authors: Cabrera
authors: L C
authors: LC
authors: Chan
authors: Z
authors: Z
authors: Chen
authors: G
authors: G
authors: Cimino
authors: J C
authors: JC
authors: Cordoba
authors: L J
authors: LJ
authors: Gu
authors: H
authors: H
authors: Hussein
authors: E
authors: E
authors: Ishii
authors: A M
authors: AM
authors: Kamel
authors: S
authors: S
authors: Labra
authors: I Q
authors: IQ
authors: Magalhães
authors: S
authors: S
authors: Mizutani
authors: E
authors: E
authors: Petridou
authors: M P
authors: MP
authors: de Oliveira
authors: P
authors: P
authors: Yuen
authors: J L
authors: JL
authors: Wiemels
authors: M F
authors: MF
authors: Greaves
mesh_terms: D000208:Acute Disease; D019677:Artificial Gene Fusion; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008431:Maternal-Fetal Exchange; D051788:Myeloid-Lymphoid Leukemia Protein; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced* / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011519:Proto-Oncogenes; D012307:Risk Factors; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C497422:KMT2A protein, human; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase