Child's direct exposure to environmental agents

Children are not simply small adults. The major difference between children and adults is the fact that children are developing and growing. Exposures to environmental agents can result in more profound consequences in a child, than a similar exposure in an adult. These environmental agents may results in mutations in genes involved in control of cell division, apoptosis (programmed cell death), growth and differentiation. Infants and children differ from adults in their exposure both qualitatively and quantitatively. They eat more food, drink more water and breathe more air per unit of body weight than adults do, and the activity patterns of children further increase their exposure to environmental agents.

  • Atmospheric pollution [Knox, 2005]
  • Electric and magnetic fields [Wertheimer & Leeper, 1979; Wartenberg D, 1998, 2001; UKCCS, 1999; Draper, 2005; Kheifets, Afifi, Monroe, Swanson, 2011]
  • Radon exposure [Tong et al., 2012]
  • Pesticides [Daniels, 1997; Landrigan, 2003]
  • Residing near nuclear power plants [Ghirga, 2010; Fairlie, 2010]
  • Atopic diseases [Wen, 2000; Manning & Carroll, 1957]
  • Infections [McKinney, 1987; Dockerty, 1999; Nyari, 2003; Cope, 2000; Dorak, 1996; Kerr, 2003; Priftakis, 2003; MacKenzie, 1999; Smith, 1999; Little J, 1999; Metayer et. al., 2013]
  • Blood levels of folate at birth [Chokkalingam et al., 2013]
  • Theories:
    • Population mixing [Kinlen, 1995; Alexander, 1997; Boutou, 2002]
    • Two-independent mutations [Greaves & Alexander, 1993]
    • Seasonality [Badrinath, 1997; Feltbower, 2001; Karimi & Yarmohammadi, 2003]
    • Pre-school day care [Dockerty, 1999; Neglia, 2000; Gilham, 2005]
    • No or little breastfeeding [Schuz, 1999; Bener, 2001; Martin, 2005]
    • Clustering [McNally, 2002; Greenberg & Shuster, 1985; Schmidt, 1998; Alexander, 1999]

Atmospheric pollution

A recent study in the UK reports associations to childhood cancer development with proximity of birth places to sites of industrial combustion, volatile organic compounds (VOCs) uses and associated engine exhausts, 1,3-butadiene, dioxins and benz(a)pyrene.

Electric and magnetic fields

Electromagnetic fields create low frequency non-ionising radiation which can cause molecular damage. Electromagnetic fields include static fields, power frequency fields, radio frequency fields and UV radiation. These fields are everywhere in modern societies. Examples of sources of exposure are production and use of electric power, electronic surveillance systems, wireless communications, tanning machines and solar exposure. The most visible source to extremely low frequency (ELF) magnetic fields is arguably power lines and in particular high voltage transmission lines. It was first pointed out in 1979 that long term-term exposure to low frequency magnetic fields (e.g., living near the power lines) may be associated with leukaemia risk in children. Further studies concluded that the data supporting residential electromagnetic fields as the principle risk factor are suggestive with small to moderate effect sizes. A study carried out in the UK in 1999 showed a trend of increasing incidence with increasing exposure but the study was not powerful enough to provide a statistically significant result. Recently, in a large case-control study it was concluded that a child’s risk of leukaemia increased steadily with proximity to high voltage power lines of the home they lived in at birth and the distance up to 600m may increase the risk.

It is now internationally agreed that the electric and magnetic fields are a possible cause for concern in humans.

An article published in 2011 reports that extremely low frequency magnetic fields such as those are produced by electric power systems may not be associated with elevated risks of childhood leukemia.

Radon Exposure

Although leukemia can be induced by Radon, it has not been consistently demonstrated. It is reported that by applying a meta-analysis, an increased risk of childhood leukemia induced by indoor radon exposure was noted for overall leukemia and for acute lymphoblastic leukemia (ALL)

Residing near nuclear power plants

It is reported that among children living within 5 km of all German nuclear power stations, there is an increased risk of cancer incidence. The article also outlines a possible biological mechanism to explain the increased cancers, suggesting that doses from environmental nuclear power plant emissions to embryos/ fetuses in pregnant women near the plants may be larger than suspected, and that hemopoietic tissues may be considerably more radiosensitive in embryos/ fetuses than in newborn babies.

It is also reported that children under five years of age living near nuclear power plants (NPPs) had an increased risk of cancer incidence. Nevertheless, other UK, France, Spain and Finland studies did not find cancer incidence and/or death increase near NPPs.

Pesticides

Associations between a child’s exposure to pesticides and childhood cancer have been reported. Certain pesticides are classified as endocrine disruptors and linked to childhood cancer development.

Atopic diseases

Studies showed contradictory associations between asthma and other allergic diseases, and leukaemia, neuroblastoma and lymphoma.

Infections

Researchers suspected that infections can be a risk to children to develop cancer. There is some evidence supporting an infectious aetiology for childhood leukaemia, particularly c-ALL but the agents involved and the precise mechanisms are unclear. Studies mainly focused on early year (birth to 12 months) exposures to certain viruses which included influenza, measles, CMV, adenovirus, parvovirus, polyomavirus-JCV, polyomavirus-BKV, polyomovirus-SV40, herpes virus, HHV-6 virus, chicken pox and mumps. The only common feature of these studies is the lack of consistency.

There is weak evidence for the involvement of infections in childhood tumours. Some studies suggest an infectious aetiology for at least some CNS tumours and osteosarcomas.

On the other hand, there is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood acute lymphoblastic leukemia (ALL).

Blood levels of folate at birth

It is reported that there is no association between birth folate concentrations and risk of childhood acute myeloid leukemia (AML) or major acute lymphoblastic leukemia (ALL) subgroups. Impact: However, they do not rule out a role for folate through exposures after birth or in early stages of fetal development.

Theories

There are various theories for the origin of infections focusing mainly on leukaemia:

Population mixing: It has been suggested that in areas where there is an influx of residents from other areas there would be an increased level of contacts between susceptible individuals and infected individuals (impaired herd immunity hypothesis). Non-exposed individuals living where the relevant infection is not endemic, subsequently become at risk when exposed by mixing with an incoming population of infected carriers. This hypothesis has been tested in the UK. Studies indicated an increased risk of ALL in such mixed populations. It is suggested that one or more specific agents are involved.

Two-independent mutation: It has been suggested for the common subtype of ALL (c-ALL) arises as a result of two independent mutations. The first (creation of pre-leukaemic clone of cells) is occurring during the pregnancy or soon after birth. The second mutation occurs after an average period of three years leading to onset of disease. It has been suggested that common childhood diseases can serve as a promoter of the second mutation. Therefore, if there is a delay in the normal pattern of exposure of the child’s immune system to common childhood infections, this delay may increase the number of susceptible cells hence increasing the risk of the second mutation. Delay in the child’s exposure to common infections might occur due to lifestyle changes associated with socio-economic development (delayed infection hypothesis). This hypothesis considers infections in general.

Seasonality: Seasonality of onset has been shown for ALL, which is presumed to be characteristics of infectious diseases.

Pre-school day care: Children are generally at risk of getting infectious diseases if they attend day care at an early age. This can be considered protective as well. No evidence has been reported to show any associations between day care attendance and leukaemia.

No or little breastfeeding: It has been reported that breastfeeding has great benefits to the infant as well as the mother. These include health, nutritional, immunologic, developmental, psychological, social, economic, and environmental benefits. Therefore, it has been hypothesised that no or perhaps little breastfeeding of the infant should expose the infant to infections by eliminating the protective effects, particularly immune stimulation, of breastfeeding. However, some studies found no or weak protective associations with childhood leukaemia whereas some others found a small but significant protective effect of breastfeeding for ALL, Hodgkin’s lymphoma and neuroblastoma.

Clustering: Researchers have been concerned for many years by the existence of clusters of childhood cancer cases, particularly of leukaemia. Hypothesis was that the clusters might point to an infectious origin to localised environmental exposures. The strongest clusters have been observed for children with leukaemia diagnosed before six years of age in the UK. However, no known cause for clustering has been identified. Speculations included population mixing and environmental pollution. It should be remembered that the clustering does not mean cases diagnosed simultaneously as in an infectious disease outbreak. Evidence for the involvement of infections in childhood tumors is weak. However, space-time clustering among childhood CNS tumors in the UK has been reported. This could support an infectious etiology for at least some CNS tumors.