Ross J A, Potter J D, Reaman G H, Pendergrass T W, Robison L L
Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, USA.
Cancer Causes Control. 1996 Nov;7(6):581-90. doi: 10.1007/BF00051700.
Nearly 80 percent of infant leukemias present with an abnormality involving the MLL gene at 11q23. Moreover, secondary acute myeloid leukemias (AML) that occur as the result of chemotherapy agents, which are known to inhibit DNA topoisomerase II, often manifest the same MLL abnormalities. It has been hypothesized that de novo infant leukemias may occur as a result of maternal exposure to agents in diet and medications that inhibit DNA topoisomerase II. Three epidemiologic studies of childhood leukemia with similar methodologies were conducted in the United States and Canada over the past 10 years by the Children's Cancer Group (CCG). Of the total 771 mothers of infants diagnosed at one year of age or less (< 12.5 months) who originally were interviewed (303 infant cases and 468 matched controls) across the three studies, follow-up questionnaire data on maternal exposure to potential DNA topoisomerase II inhibitors during pregnancy were available on 84 cases and 97 matched controls in the US. For maternal diet, a composite variable was created that consisted of 10 foods identified alpha 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 stratum, there was a statistically significant positive association (P trend = 0.04) with increasing consumption of DNA topoisomerase II-inhibitor containing foods (odds ratio [OR] = 9.8, 95 percent confidence interval [CI] = 1.1-84.8; OR = 10.2, CI = 1.1-96.4; for medium and high consumption, respectively). Other potential topoisomerase II inhibitors were explored; no significant findings were found. Results of this preliminary study, in combination with molecular data, should be used in future investigations of childhood leukemia (particularly, infant) to justify the incorporation of a detailed dietary history.
近80%的婴儿白血病存在涉及11q23处MLL基因的异常。此外，作为已知可抑制DNA拓扑异构酶II的化疗药物所致的继发性急性髓系白血病（AML），常常表现出相同的MLL异常。据推测，原发性婴儿白血病可能是由于母亲在饮食和药物中接触了抑制DNA拓扑异构酶II的物质所致。在过去10年里，儿童癌症组（CCG）在美国和加拿大开展了三项采用类似方法的儿童白血病流行病学研究。在这三项研究中，最初接受访谈的一岁及以下（<12.5个月）确诊婴儿的771位母亲中（303例婴儿病例和468例匹配对照），在美国有84例病例和97例匹配对照可获得关于孕期母亲接触潜在DNA拓扑异构酶II抑制剂的随访问卷数据。对于母亲的饮食，创建了一个综合变量，该变量由事先确定的10种含有DNA拓扑异构酶II抑制剂的食物组成。对于总体组或急性淋巴细胞白血病（ALL）亚组，随着母亲摄入量增加均无显著趋势。然而，在AML亚组中，摄入含DNA拓扑异构酶II抑制剂食物量增加存在统计学显著的正相关（P趋势 = 0.04）（优势比[OR] = 9.8，95%置信区间[CI] = 1.1 - 84.8；对于中等和高摄入量，OR分别为10.2，CI = 1.1 - 96.4）。还探究了其他潜在的拓扑异构酶II抑制剂；未发现显著结果。这项初步研究的结果，结合分子数据，应用于未来儿童白血病（尤其是婴儿白血病）的调查中，以证明纳入详细饮食史的合理性。
