Parental Pesticide Exposure and Childhood Brain Cancer

Parental Pesticide Exposure and Childhood Brain Cancer: History

Please note this is an old version of this entry, which may differ significantly from the current revision.

Subjects: Allergy

Contributor: Aiza Khan

There is an association between childhood brain tumors (CBT) and parental pesticides exposure before childbirth, after birth, and residential exposure. It is in line with the International Agency for Research on Cancer (IARC) Monograph evaluating the carcinogenicity of diazinon, glyphosate, malathion, parathion, and tetrachlorvinphos.

children
cancer
brain

1. Introduction

Cancer is one of the most important causes of death in childhood in developed countries. In particular, childhood brain tumors (CBT) are the second most common pediatric cancer [1]. Despite the ongoing research, the etiology of this fatal tumor remains unknown. The most recent genomic and molecular analysis of the CBT’s biology, management, and prognosis has been impressive, with neuropathological classification linked to molecular biology results [2,3,4,5]. Most of the molecular subgroup-specific outcome data in CBT are generated from retrospective studies on heterogeneously treated children. It will be crucial to prospectively evaluate the clinical implications of genomic and molecular data in the context of therapeutic trials before the conventional clinical implementation.

Some of the factors that have been established include a few underlying genetic syndromes and ionizing radiation [6]. However, evidence regarding other potential risk factors, including pesticides exposure, carcinogen-metabolizing genes, and viruses, is limited and/or conflicting [7,8,9].

Several case-control studies on the effect of pesticide exposure on CBT have yielded mixed results [10,11,12]. In addition, the meta-analyses on the impact of pesticides on CBT have often recommended caution in interpreting results due to the possible implications of some potential confounding factors [13]. Hence, additional information reflecting a diversity of exposure situations will be more revealing to strengthen the existing findings.

A pesticide is a term used to describe a substance or mixture of substances essentially used to destroy, repel, or mitigate any pest. Commonly, pesticide use is considered more related to agriculture, and children living on or near farmlands are likely to be exposed through a number of mechanisms that include agro-industrial application drift, overspray, and dust brought inside homes on shoes of parents [14]. Another potential exposure involves urban settings when pesticides are used for lawn/garden care [15,16]. In addition, several studies have elucidated that various factors may increase the exposure to pesticides at home. These factors include inadequate or excessive application of pesticides and improper washing of pesticide-treated bedding. Therefore, children are likely to get exposed to pesticides, either breathing in or eating them [17,18,19,20,21,22,23].

2. Parental Pesticide Exposure and Childhood Brain Cancer

There is an association between CBT and parental exposure to pesticides, mainly when exposure to pesticides occurs before and after birth. In addition, parental exposure to pesticides in household settings is more strongly associated with CBT than parental occupational exposure to pesticides. Farm residence can be used as a proxy measure for occupational and residential pesticide exposures, although it does not indicate the direct exposure of an individual [10]. It is paramount to remember that various potential carcinogens can be associated with farm life, and some have been extensively revised [55,56,57,58,59]. It is difficult to assess on several occasions if it is the exposure to animals, exposure to pesticides, or the combination of more than one factor that is more likely to be linked with CBT. For instance, pesticide-related to farms has been associated with cancer development, but farm animals and pets have been reported as a potential risk factor for CBT. Although the gut microbiome is influenced by the contacts with pets and may play a protective role, one substantial risk related to animal contact is getting exposed to animal viruses, such as coronaviruses. Since RNA viruses and DNA viruses have induced brain tumors and hematological and cardiac neoplasms [40,60], it may be plausible that COVID-19 may cause hyperactivation of immune cells, resulting in chronic inflammation, which may act as promoting factor. In some settings, it may induce the reawakening of dormant cancer cells such as neutrophil extracellular traps [61].

The pest control treatments at home may be associated with the increased risk of CBT. However, looking at the individual studies, the residential pesticide appears to be different by the type of application. The method of application (professional extermination vs. non-professional application) also plays an essential role in the causation of CBT. Studies emphasizing pesticide application’s exact circumstances, including the types of personal protective equipment involved, may be important. The use of hand gloves at pesticide application, for instance, can be critical, as suggested by the Agricultural Health Study of the children of Iowa pesticide applicators in the USA. Although there was no association between parental exposure to pesticide application and the risk of childhood cancer in that study, parent applicators who did not use chemically resistant gloves ended up having children at higher risk of childhood cancer than those who used gloves [63]. Parental exposure to pesticides has been demonstrated to be strongly associated with this tumor. Previous meta-analyses have investigated a reasonably consistent link between pesticide exposure and CBT development [35,36,38,64]. Furthermore, the most significant risks of CBT appear to be associated with household insecticide use as well as prenatal exposure to insecticides [35]. In addition, it was also suggested that genetic susceptibilities might have a role in determining the effects of childhood pesticide exposures, and thus recommended future studies to examine the role of gene-environment interactions in the development of CBT [65]. Also, it was investigated that children, when exposed to insecticides, were more likely to develop brain tumors if they also carried PON1_C-108T SNP (single nucleotide polymorphism of the paraoxonase—PON1 gene) [10]. Constitutive, genetic variation influences insecticide metabolism, and Searles Nielsen et al. [46] also examined whether CBT is associated with this SNP. They found no association between CBT and the single coding region SNP PON1_Q192R but a strong dose–response relationship between CBT and PON1_C–108T, a promoter-region SNP associated with enzyme levels [46]. These authors also reported that genotype and insecticide interactions occur during childhood but usually not during pregnancy. In fact, it seems that during prenatal development, maternal enzymes serve as the first line of defense against exogenous exposure. Thus, even though they do not suggest a lack of effect of insecticide exposure during this potentially sensitive period, they emphasize the lack of synergism with fetal genotype.

In a population-based case-control study done between 1978–1990, the purpose of which was to determine if CBT is associated with some functional genetic polymorphisms, the researchers found no biologically plausible main effects for any of the metabolic polymorphisms with CBT risk. They noticed strong interactions between genotype and insecticide exposure during childhood. These interactions were present among both Hispanic and non-Hispanic white children. Similar results were also observed with two other gene variants, FMO1_C-9536A and BCHE_A539T. The latter is thought to affect the ability to detoxify organophosphorus and/or carbamate insecticides [39]. Hence, it further emphasizes that genetic susceptibility is an essential factor in the exposure of pesticides and CBT development.

Global and concerted actions to raise awareness of CBT risk and pesticide exposure are worthwhile. For instance, experts from countries already met at the international level to assess the carcinogenicity of the organophosphate pesticides, which include tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate [25,67,68,69,70,71,72]. In the future, it will be more helpful to focus on parental exposure and pediatric cancer while emphasizing evidence-based, proactive measures such as the wearing of chemical-resistant gloves during pesticide application.

In conclusion, results support an association between pesticide exposure and CBT. If it occurs before or during pregnancy and in early childhood, the pesticides exposure is more likely to contribute to developing cancer of young/adult brain tumors. Additionally, studies strongly support that pesticide exposure via household plays a role in CBT development. Because of the etiologic complexity of brain tumors, it is highly recommended that future studies be extensive, and investigations with transgenic animal models may be useful. Moreover, enhanced methods for exposure assessment, time window of the stage of human development, and pesticide application methods will be required.

Additionally, awareness and education programs regarding the harmful effects of pesticide exposure on health may benefit the population. Residential use of pesticides should be carried out with all precautions to minimize exposure. Until more extensive studies are performed to confirm the results, all efforts should be maximized to limit children and adults’ exposure to pesticides.

This entry is adapted from the peer-reviewed paper 10.3390/children8121096

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