Maternal Exposures and Risk of Infant Acute Leukemia in Brazil.

Associations between some environmental exposures and IAL with MLL rearrangements have been pointed out in the literature. We performed an investigative analysis to determine the frequency of MLL gene rearrangement in IAL in order to explore the risk factors for maternal exposure to DNA-damaging substances. Three different methods to detect the possible abnormalities involving this gene were used during a Brazilian epidemiological study: conventional karyotyping, RT-PCR assay, and FISH. The distribution of ALL and AML cases was very similar with respect to gender, age and region of residence at the time of diagnosis, and it was possible to study the MLL status in 198 of these cases. A statistically significant association was observed between pro-B ALL and MLL^+ve cases and also, the age group 0–2 months was associated with MLL^+ve cases, as expected. The FISH technique was clearly the most efficient one to detect the rearrangements, followed by RT-PCR assay. The maternal exposure data were obtained from cases and controls by interview, using a structured questionnaire. Up to now, 171 incident IAL cases were eligible for the study and 379 aged-frequency matched controls showing severe no-neoplasic diseases in the same regions were retrieved and their respective mothers interviewed. Intrauterine and childhood exposure to medicines, pesticides and other chemicals, smoking, alcohol intake, pets and reproductive antecedents were ascertained for both groups. A high frequency of molecular MLL^+ve (84,4%) and other chromosomal abnormalities were found. A statistically significant association with MLL^+ve was observed for pesticides exposure at home (OR 2.38, 95% CI, 1.27–3.96), and intake of hormones during the first weeks of pregnancy (OR 5,93 CI, 2,05–17,11) p=0,001. Statistically no significant increased risks were seen for urban families (OR 1.33, 95% CI, 0.70–2.52), metronidazol (OR 1.31, 95% CI 0.58–2.95) and dipirona (OR 1.51, 95% CI 0.85–2.68). It is therefore important that the associations observed in this study regarding hormone in taking should be re-evaluated in an extended case-control study. In view of the association recently reported between MLL^+ve infant leukaemia and lack of function NQ01 alleles, screening for metabolic polymorphisms involved in carcinogen metabolism should also be included in subsequent studies.