Infant Acute Leukemia and Maternal Exposures during Pregnancy

Abstract

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)(2000)(2001)(2002)(2003)(2004)(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. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2336 -41)

Exposições ambientais e leucemias na infância no Brasil: uma análise exploratória de sua associação

“…Os resultados encontrados na presente investigação são apoiados por relatos de outros estudos, os quais mencionam as possíveis contribuições das exposições químicas na gravidez, hábitos de vida e consumo de serviços de saúde durante a gestação, todas estas de relevância para a saúde do recém-nascido, bem como no processo de carcinogênese (IARC, 1987;POMBO-DE-OLIVEIRA;KOIFMAN, 2006;SHU et al, 2002;INFANTE-RIVARD et al, 2003;KINLEN, 1995;MCNALLY et al, 2004;WEN et al, 2002;PANG et al, 2003;RUDANT et al, 2007). Neste sentido, os resultados apresentados nesta investigação reiteram a contribuição das exposições ambientais analisadas de forma conjunta, e não apenas individualizada, no desenvolvimento das leucemias na infância.…”

“…Outro estudo caso-controle acerca das exposições maternas durante a gestação e as leucemias na infância, realizado na população brasileira, indicou aumento de 40% no risco para o desenvolvimento das leucemias na infância com antecedentes de uso de dipirona no perí-odo gestacional (POMBO-DE-OLIVEIRA; KOIFMAN, 2006). Este mesmo estudo apontou associação positiva entre o uso de pesticidas domésticos durante a gestação e discreta elevação estatisticamente significativa (18%) no risco de leucemias na infância.…”

“…Dentre estes, destacam-se a exposição a substâncias químicas (IARC, 1987;POMBO-DE-OLIVEIRA;KOIFMAN, 2006), radiações ionizantes e não-ionizantes (BELSON et al, 2007;SHU et al, 2002;WAKERFORD et al, 2003;WERTHEIMER;LEEPER, 1979;INFANTE-RIVARD et al, 2003), infecções (KINLEN, 1995;MCNALLY et al, 2004;DICKINSON, 2005) …”

Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

“…Parental exposures to environmental hazards or use of parental medication have been reported to contribute to ALL risk. [14][15][16][17][18] Given the possible role of parental factors in disease susceptibility, focusing solely on the genotype of the child in ALL association studies may be insufficient to fully address disease etiology. 19 The accumulated experience to date and relative lack of success of initial efforts to identify novel ALL predisposition loci emphasize the need for alternative study designs and methods.…”

Selection bias in case–control studies on household exposure to pesticides and childhood acute leukemia

“…Items 1-4: Concurrent Selection of Controls, Age Matching, Inclusion, and Exclusion Criteria for Cases and Controls, Exclusion Criteria for Hospital Controls In four studies, two hospital-based (Schwartzbaum et al, 1991;Pombo-de-Oliveira and Koifman, 2006) and two populationbased (Infante-Rivard et al, 1999;Ma et al, 2002) studies, controls were selected concurrently with respect to the time of case diagnosis. Yet, in the two hospital-based studies, the authors did not mention if cases and controls both had to reside in the same hospital catchment area.…”