Infant Acute Leukemia and Environmental Exposures During Pregnancy

Abstract

MAA2-PD-08 Introduction: The understanding of leukemogenic pathways in childhood has been improved markedly by a series of critical and consistent identified mutations occurring during pregnancy. A critical unsolved issue is the cause of these genetic alterations and, in this respect, the different pediatric leukemia subtypes might have distinct etiologies. Most cases of infant acute leukemia (IAL) have rearrangements of the MLL gene at region 11q23 and arise in utero. Acute leukemia in infants (IAL) has a unique profile characterized by the high incidence of translocations involving MLL gene located at 11q23 region. To test the potential role of intrauterine and perinatal factors linked to the risk of IAL development, we conduced a hospital-based case–control study in different cities of a developing country. Methods: A total of 202 children (0–21 months old) with newly diagnosed IAL were enrolled between 1999 and 2005, and 440 age-matched controls were selected from the same hospitals wherein IAL cases were treated. A case-only study approach was used to test the interaction effects between environmental exposures during pregnancy (hormones, dipyrone, metronidazole, and misoprostol) and MLL gene rearrangements. Results: A statistically significant association between maternal use of hormones during pregnancy and IAL, adjusted for sex, income, maternal age, cancer antecedents, and birth weight, was observed (odds ratio [OR] = 8.70, 95% confidence interval [CI] = 2.76–27.43). Interaction odds ratios between MLL status and maternal exposures were the following: dipyrone (OR = 1.53; 95% CI = 0.75–3.08), metronidazole (1.97; 0.69-5.64), and quinolones (2.63; 0.23–30.21). Discussion: This study aimed to evaluate the association between environmental exposures during pregnancy and IAL, and a marked statistically significant high risk was observed for hormonal exposure during pregnancy. Previous studies support the hypothesis that IAL with MLL rearrangements could be caused by in utero environmental exposures that could inhibit topo II activity. Several malignant diseases result from interactions between environmental and individual genetic variations and, efforts have been conducted that aim to identify susceptibility genes or linked polymorphism markers that would have contributed to these investigations. The present study provides evidence that hormones exposure during pregnancy should be studied as a possible risk factor associated to in utero leukemogenesis. Conclusion: The strong and statistically significant association between IAL and estrogen exposure during pregnancy suggests a possible component involved in intrauterine leukemogenesis.