Alexander F E, Patheal S L, Biondi A, Brandalise S, Cabrera M E, Chan L C, Chen Z, Cimino G, Cordoba J C, Gu L J, Hussein H, Ishii E, Kamel A M, Labra S, Magalhães I Q, Mizutani S, Petridou E, de Oliveira M P, Yuen P, Wiemels J L, Greaves M F
Department of Public Health Science, University of Edinburgh, United Kingdom.
Cancer Res. 2001 Mar 15;61(6):2542-6.
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.
婴儿急性白血病（IAL）常涉及MLL基因与几种潜在伙伴基因之一的断裂和重组。这些基因融合在子宫内就已出现，与拓扑异构酶II（topo-II）抑制剂化疗后继发的白血病中发现的基因融合相似。这导致了一种假说，即子宫内接触化学物质可能通过对topo-II的影响而导致IAL。我们报告了一项针对不同国家和种族群体的IAL病例对照试点研究。大多数中心的病例（n = 136）是基于人群的。对照（n = 266）从服务相同人群的医院的住院患者和门诊患者中选取。通过Southern印迹分析得出MLL重排状态，并使用结构化问卷通过访谈获得母亲的接触数据。除了吸烟和饮酒外，很少有母亲报告接触过已知的topo-II抑制剂。在摄入几类药物（包括草药和归类为“DNA损伤性”的药物）以及接触杀虫剂方面，病例对照之间存在明显差异，后两者分别主要归因于一种非甾体抗炎药双氯芬酸和灭蚊剂（包括拜戈）。MLL阳性（而非MLL阴性）白血病的比值比升高（DNA损伤性药物为2.31，P = 0.03；双氯芬酸为5.84，P = 0.001；灭蚊剂为9.68，P = 0.003）。虽然目前尚不清楚这些特定接触是否通过对topo-II的影响起作用，但数据表明孕期胎儿接触特定化学物质可能导致MLL基因融合。鉴于双氯芬酸、拜戈和其他氨基甲酸酯类杀虫剂在某些环境中的广泛使用，迫切需要证实这些明显的关联。
