ReviewResidential exposure to pesticides and childhood leukaemia: A systematic review and meta-analysis
Introduction
For years, pesticides have been widely used against insects, fungi, rodents, noxious weeds, etc. that can damage crops, property and human health. As with any biologically active agents, pesticides may, however, have unwanted side-effects, including cancer.
Children can be exposed to pesticides from various sources at different levels than adults under the same exposure scenario.
The first possible source of exposure to pesticides in childhood is indirect contamination from parental occupational exposure. Children can also be directly exposed to pesticides from indoor uses (in homes, schools, and other buildings), from outdoor uses (garden, playing areas/public lands, agricultural application drift, overspray or off-gassing), through contaminated food and drinking water, by handling treated or contaminated pets or others (e.g. through the use of insecticidal shampoos for lice infestation) (Zahm and Ward, 1998).
Children may be especially vulnerable to adverse health effects of pesticides due to both developmental (physiological) and behavioural factors that can increase the dose and toxicity as compared with adults who live in the same environment (Bearer, 1995, Bruckner and Weil, 1999, Karr et al., 2007, Moya et al., 2004). Air concentrations of pesticides have been found to be higher closer to the floor (Fenske et al., 2000). As children are low to the ground, they may have greater exposure to volatile pesticide vapours. Their metabolism is also significantly different from that in adults, resulting in different levels of toxic metabolites in foetus and young children compared with adults (Garry, 2004, Weiss et al., 2004). Their immune system is also less mature.
It has long been recognised that childhood leukaemia is not a homogeneous disease. Acute leukaemia deriving from the lymphocytic or from the myeloid lineage are by far the most frequently observed among children. The most common type is acute lymphocytic (or lymphoblastic or lymphoïd) leukaemia (ALL) which accounts for 75–80% of all cases of childhood leukaemia. Acute myeloïd (myelocytic, myelogenous or non lymphoblastic) leukaemia (AML), also termed acute non lymphoblastic leukaemia (ANLL), is less frequent (about 20%). The chronic forms, chronic myeloïd leukaemia (CML) and chronic lymphocytic leukaemia (CLL), are rarely seen during childhood (Belson et al., 2007, Onciu and Pui, 2006). This major morphological division is supplemented by the identification of a range of subsets based on gene expression, antigens that delineate cell type or differentiation status, and chromosomal and molecular abnormalities. Leukaemia is a clonal disease (originating in a single cell) evolving by the accrual of mutations within a clone. There is now compelling evidence that the first or initiating event in leukaemia is a chromosome translocation occurring during foetal development but one or more additional postnatal genetic alterations are needed for leukaemia development (Greaves, 2002).
The aetiology of childhood leukaemia remains largely unknown. The difficulty arises from the fact that paediatric leukaemias, like most cancers, have multifactorial aetiologies involving the interaction between various aspects originating from the environment as well as human genetics. In addition, the investigation of childhood leukaemia requires cognizance of the timing of exposure, regardless of its environmental and molecular origins (Buffler et al., 2005). Epidemiological studies on acute leukaemia in children have examined possible risk factors including genetic, infectious and environmental factors (e.g., ionizing radiation, non-ionizing radiation, electromagnetic fields, cigarette smoking, alcohol consumption, hydrocarbons, and pesticides). So far ionizing radiation has been the most significantly linked with either ALL or AML. The strongest evidence of an association with AML has been found for benzene and cytotoxics (alkylators and topoisomerase II inhibitors). Most other factors have been weakly or inconsistently associated with either forms of childhood leukaemia (Belson et al., 2007, Eden, 2010, Linet et al., 2003). Among environmental chemicals, pesticides have been specifically scrutinized. There is growing evidence in support of an association between pesticides exposure and childhood leukaemia. Most of the studies evaluating exposure to household pesticides suggest that an increased risk is associated with in utero and postnatal pesticide exposures, although the subtype of leukaemia, definition of exposure, and exposure period at risk differ among these studies (Buffler et al., 2005).
Several literature reviews on pesticides exposure and childhood cancers have been published recently (Infante-Rivard and Weichenthal, 2007, Metayer and Buffler, 2008, Nasterlack, 2006, Nasterlack, 2007). These authors considered that investigating in the acquisition and critical review of exposure information was a crucial step for establishing causal association. Suggestions for future work on chemical risk factors and childhood leukaemia included the need of pooling data and analyses as well as carrying out in-depth reviews of studies with the goal of understanding the reasons for discrepant results (Infante-Rivard, 2008). In the last months, systematic reviews and meta-analyses have been conducted with regard to childhood leukaemia and parental occupational exposure to pesticides (Van Maele-Fabry et al., 2010, Wigle et al., 2009). Both meta-analyses concluded that the strongest evidence of an increased risk of childhood leukaemia comes from maternal occupational exposure to pesticides, the associations with paternal exposure being weaker and less consistent.
The purpose of the present study is to perform a systematic review and meta-analysis of published studies that have examined the association between residential exposure to pesticides and leukaemia among children with the aim to enhance our understanding of the potential involvement of such exposure in the aetiology of childhood leukaemia. To this end, our review focuses on several exposure issues distinguishing the sources of pesticide exposure (indoor and outdoor use of pesticides) as well as the critical exposure windows including prenatal and postnatal exposures. A biocide category-specific approach is also followed in an attempt to identify whether specific category(ies) is(are) predominantly involved. Finally, as a common cause for all types and subtypes of childhood leukaemia is highly unlikely (Rossig and Juergens, 2008), an attempt is made to assess the results according to the type of leukaemia.
Section snippets
Study identification
An electronic search on PubMed (National Library of Medicine, Bethesda, MD) was conducted for the period 1966 to 31 December 2009. Various combinations of the following key words were used: pesticide, biocide, insecticide, fungicide, herbicide, rodenticide, pets insecticides, (professional) pest control, environmental exposure, environmental pollutants, child, children, childhood, infant, newborn, preschool child, adolescent, youth, teenager, leukaemia, myeloid, myeloblastic, myelogenous,
Literature selection and study characteristics
More than 1500 articles were retrieved from MEDLINE and hand searching in the reference lists of the relevant publications. We reduced these to a list of 261 potentially relevant studies. The majority of these studies (N = 240) were excluded because they were not in English (N = 16), were of a design other than case-control or cohort (N = 114), concerned occupational exposure (N = 27), dealt with risk assessment, exposure assessment or methodology (N = 30), dealt with data for teenagers mixed with data
Summary of evidence
This systematic review and meta-analysis examined the relevant epidemiological studies reporting an association between residential exposure to pesticides and childhood leukaemia. Overall, residential use of pesticides was associated with childhood leukaemia. The increased risk was statistically significant and did not vary substantially when omitting extreme value studies (estimators of relative risk or study weight). This conclusion is consistent with the results of narrative reviews (Daniels
Conclusions
Overall, the present MA provides quantitative evidence to consider residential exposure to pesticides as a contributing risk factor for childhood leukaemia. The strongest associations were observed for exposure during pregnancy. Risk estimates were the greatest for indoor exposure as well as for insecticides. As the development of childhood leukaemia is probably multifactorial, there is a need for additional studies to assess gene–environment interactions and to correlate improved exposure data
Role of the funding source
Van Maele-Fabry Geneviève was supported by a grant from the Belgian Ministry of Health (Grant Number 95/15 (164)).
Conflict of interest statement
There are none.
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