Infant acute leukemia and maternal exposures during pregnancy.
Infant acute leukemia (IAL) has a unique profile characterized by the high incidence of translocations involving the MLL gene located at the 11q23 region. To test the potential role of intrauterine and perinatal factors linked to the risk of IAL development, a hospital-based case-control study was conducted in different cities of Brazil. A total of 202 children (ages 0-21 months) with newly diagnosed IAL was enrolled (1999-2005), and 440 age-matched controls were selected from the same hospitals wherein IAL cases were treated. A statistically significant association between maternal use of hormones during pregnancy and IAL was observed [odds ratio (OR), 8.76; 95% confidence interval (95% CI), 2.85-26.93] in a multivariable analysis. The association of certain exposures during pregnancy (hormones, dipyrone, metronidazole, and misoprostol) and MLL gene rearrangements was tested using a case-case approach. Despite the lack of statistical significance, the magnitude of the OR for maternal exposure to dipyrone (OR, 1.45; 95% CI, 0.75-2.86), metronidazole (OR, 1.72; 95% CI, 0.64-4.58), quinolones (OR, 2.25; 95% CI, 0.70-25.70), and hormones (OR, 1.88; 95% CI, 0.50-7.01) may suggest the occurrence of interactions between such maternal exposures during pregnancy and MLL rearrangements, yielding into IAL development. The strong and statistically significant association between IAL and estrogen exposure during pregnancy observed in this study deserves further investigation to investigate its role in intrauterine leukemogenesis.
Pombo-de-Oliveira
Maria S
MS
Instituto Nacional de Câncer, Centro de Pesquisa, Rua André Cavalcanti 37, CEP 20231-050, Rio de Janeiro, Brazil. mpombo@inca.gov.br
Koifman
Sergio
S
D000208:Acute Disease; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006761:Hospitals; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014178:Translocation, Genetic
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase