Spector Logan G, Xie Yang, Robison Leslie L, Heerema Nyla A, Hilden Joanne M, Lange Beverly, Felix Carolyn A, Davies Stella M, Slavin Joanne, Potter John D, Blair Cindy K, Reaman Gregory H, Ross Julie A
Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):651-5. doi: 10.1158/1055-9965.EPI-04-0602.
The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+).
This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression.
There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-).
Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.
MLL 11q23易位发生于子宫内，存在于75%的婴儿白血病中。MLL+急性髓系白血病（AML）可在使用DNA拓扑异构酶II（DNAt2）抑制剂化疗后发生，这表明这些也天然存在于食物中的物质可能与婴儿白血病有关。我们假设母亲在孕期食用膳食DNAt2抑制剂会增加婴儿患白血病的风险，尤其是AML（MLL+）。
这项儿童肿瘤学组的病例对照研究包括1996年至2002年期间诊断出的240例婴儿急性白血病[AML和急性淋巴细胞白血病（ALL）]新发病例以及255名通过随机数字拨号选取的对照。通过食物频率问卷确定母亲孕期的饮食情况。创建了一个包含事先确定含有DNAt2抑制剂的特定食物以及蔬菜和水果的指数，并使用无条件逻辑回归进行分析。
几乎没有证据表明特定的DNAt2指数与总体白血病及其亚型之间存在关联。AML（MLL+）是个例外；将第二至第四四分位数与第一四分位数进行比较的优势比（95%置信区间）分别为1.9（0.5 - 7.0）、2.1（0.6 - 7.7）和3.2（0.9 - 11.9）（趋势P值 = 0.10）。对于蔬菜和水果指数，所有白血病合并、ALL（MLL+）和AML（MLL-）均存在显著或接近显著的负线性趋势。
总体而言，母亲在孕期食用新鲜蔬菜和水果与婴儿患白血病风险降低有关，尤其是MLL+。然而，对于AML（MLL+）病例，母亲食用特定的DNAt2抑制剂似乎会增加风险。尽管基于样本量较小，但这些数据为婴儿白血病不同的病因途径提供了一些支持。
