Childhood leukemia is the most common type of cancer among children, accounting for one-fourth (25.2%) of all pediatric cancers. Despite declines in mortality, pediatric leukemia incidence in the U.S. has increased 20% from 1975--1995. Four decades of epidemiological research has identified few undisputed risk factors, except genetic syndromes and high dose radiation. Various environmental exposures have been associated with childhood leukemia, although their exact etiologic role is still unclear. One of the limitations of prior studies is that to date, few studies have focused on an individual's ability to metabolize and eliminate chemical carcinogens. Individuals who are less effective at eliminating these environmental insults may be more susceptible to developing cancer, including pediatric leukemia.; To address these concerns, a retrospective age-race-gender matched case-control study was conducted among children residing in Western Pennsylvania during a six-year study period (1995--2000). Interviews were conducted with the mothers of cancer cases and controls to obtain demographic, medical, and lifestyle information, as well as pesticide use history. DNA was collected via buccal swabs to assess presence of CYP1A1 and GSTM1 polymorphisms.; Maternal exposure to dental x-rays during either the preconception or pregnancy time periods were significantly associated with an increased risk of childhood leukemia among offspring; the association was even stronger when the analysis was restricted to the pregnancy time period only although the results were of borderline significance. Maternal use of antibiotics during the index child's pregnancy was significantly associated with an almost four-fold increase in leukemia risk. Yard pesticide use during the pregnancy was significantly associated with a two-fold increase in the risk of childhood leukemia.; After incorporating the presence of CYP1A1 m4 mutation and GSTM1 null phenotype into regression models with these exposures, the odds ratios associated with antibiotic use increased to nearly 6-fold and remained statistically significant. These results suggest that exposures to potential carcinogens during the pregnancy period may confer the greatest risk for childhood leukemia and the risk may increase when the ability to eliminate reactive intermediates is compromised. Future studies may want to focus on exposures sustained during the pregnancy, to further delineate fetal susceptibility to environmental carcinogens.
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