Cancer and Immunological Effects

Carcinogenic Exposures

The third area where research remains inconclusive concerns the range of agents that contribute to cancer risk among children. For a substance to cause cancer that appears in childhood it must operate with a relatively short latency period. Because children don't have the same opportunity to develop the lifestyle choices that increase risk of cancer in adults, we can say with greater certainty that most childhood cancer is likely explained by involuntary exposure to environmental agents, narrowly defined. There are relatively few well-established environmental exposures clearly associated with pediatric cancers.

"The lifestyle of toddlers has not changed much over the past half century. Young children do not smoke, drink alcohol, or hold stressful jobs. Children do, however, receive a greater dose of whatever chemicals are in air, food, and water because, pound for pound, they breathe, eat, and drink more than adults do. . . They are also affected by parental exposures before conception, as well as by exposures in the womb. "29
(Sandra Steingraber, PhD)

All of us are likely exposed to countless carcinogens throughout our lives. Some of these are naturally occurring substances or agents, such as solar radiation, radon or carcinogens found in foods, such as aflatoxins, the toxic mould often found in peanuts, peanut butter, corn and cheese.30 Others are natural substances that become carcinogenic to humans through activities such as extraction, refining and use in the manufacture of various products.

Asbestos, arsenic, uranium, silica and nickel are all examples of such carcinogens.31 The category of carcinogens, however, that has evoked considerable attention, especially for their ability to cause cancer in childhood, includes synthetic chemicals used in plastics, pesticides, dyes and pharmaceuticals, representing many hundreds of different agents or substances.

It is beyond the scope of this document to adequately outline how carcinogenicity is determined and what substances are deemed to be carcinogenic to humans. It is useful, however, to understand that environmental hazards or agents are generally classified, according to the strength of the scientific evidence and according to scientific opinion, into one of four categories:32

Group 1. Sufficient evidence of carcinogenicity

Group 2a. Probable carcinogens
Group 2b. Possible carcinogens

Group 3. Not classifiable as to carcinogenic risk to humans (due to inadequate evidence)

Group 4. Probably not carcinogenic to humans

Of the many thousands of chemicals in current use, there are relatively few where there is sufficient toxicological information to definitively characterize cancer-causing ability (i.e., Group 1 carcinogens) in humans. In the context of childhood cancers, the data gaps are considerable. Although a number of etiological agents have been proposed as causal for different types of childhood cancer, very few have been confirmed.

The environmental carcinogens that are known to cause childhood cancers include some medications such as diethylstilbestrol and chemotherapeutic drugs, radiation and certain industrial and agricultural chemicals.34 Here we discuss in further detail only the environmental exposures linked to cancer in the young.

Radiation

Several forms of high frequency radiation (including ultraviolet, roentgen and gamma rays) are well-established human carcinogens. Radiation induces cancer primarily via damage to DNA, but there is some evidence that immunosuppression may be the mechanism involved in some cancers.35 There is some evidence that children are more susceptible to the effects from radiation than are adults.36

Evidence from high dose exposure circumstances (e.g., radiotherapy for other cancers, atomic bomb survivors) clearly indicates the link to a number of different cancers in children. Ten years after the Chernobyl accident, for example, there are published reports of increased frequency of thyroid cancer in children living or born in the areas with highest exposure to radioactive contamination.37 Leukemia is another childhood cancer associated with postnatal exposure to ionizing radiation. There is increased risk of developing additional secondary cancers after radiotherapy treatment for Hodgkin's disease.38

The effects of exposure to lower dose radiation are less clear and somewhat more controversial.39 Several case-control studies indicate that prenatal exposure to X-rays is linked with moderate increases in leukemia in children. For example, a study of twins demonstrated double the risk of leukemia in those irradiated prenatally compared to those who were not irradiated.40

Paradoxically, cohort studies following children exposed to radiation from nuclear weapons testing have not shown the expected increase in childhood leukemia.41 Radon, a naturally occurring radioactive decay product of radium that can be found in air and groundwater, is linked to lung cancer in adults. One study has reported a dose-related association between radon levels in drinking water and elevated leukemia in children; however, there is clearly need for further study of this relationship.42

Several studies have attempted to explore the possibility that parental, specifically paternal, preconceptional exposure to ionizing radiation carries a greater risk of offspring developing leukemia in childhood, but the interpretation of results has been problematic.43 Many of these studies have had only small numbers of cases to examine, and because study fathers were frequently highly exposed throughout their child's life, it was difficult to pinpoint the exact timing of the relevant exposure.44

Electromagnetic Fields (EMFs)

Electric and magnetic fields, or EMFs, are low frequency currents associated with electricity. People are exposed to EMFs from multiple sources, including electrical transmission and distribution lines and a variety of electrical appliances found in homes, schools and the workplace. There has been great public concern and controversy surrounding the hypothesis of associations between EMF exposure and brain cancer and leukemia in children. The suggestion that EMFs were linked with excess risk of cancer came initially from studies of occupationally exposed adults in whom there were modest increases in some rare cancers. The potential for this association to be causal has been vigourously debated in scientific circles.

Since the first study reporting an association between childhood cancer and EMF exposure, several other researchers have attempted to duplicate these results; however, there has been little consistency. A 1997 review and meta-analysis by the National Research Council of eleven such epidemiological studies proposed that while there is some evidence for a positive association between exposure to high magnetic fields and childhood leukemia, data are inadequate to reach a firm conclusion.45

Analysis of studies since the NRC review has not significantly changed the conclusions; however, Loomis and colleagues stress that no study has shown definitively that magnetic fields are not carcinogenic.46 As a result, some sources suggest that people adopt prudent avoidance of excess exposure to EMFs, particularly with respect to children.47

Organic Solvents

Organic solvents are major industrial chemicals that, because of their presence in many products used in homes, schools and workplaces, are potentially abundant in the environment. They are also known as volatile organic compounds (VOCs) because of their tendency to evaporate at room temperature. As a result, breathing in air that is contaminated with organic solvents is how people are most often exposed.48

The vast majority of epidemiological studies that assess carcinogenicity concern solvents as a group, with few identifying specific solvents that increase cancer risk. There is fairly consistent evidence that occupational exposure to solvents in parents (the father in particular) is associated with increased risk of brain and urinary tract cancers and leukemia in their children.49 Children may be exposed to these chemicals when they are transferred home on parent's clothing or skin, or via exhaled breath or breast milk.50

Benzene is one organic solvent that has been specifically linked to higher rates of leukemia in the offspring of exposed parents. There are strongest associations for fathers exposed to gasoline, which is the prime source of environmental benzene.51 Benzene is a known carcinogen in adults and has been shown to cause chromosomal abnormalities and changes in blood-forming cells in the liver and spleen of fetal mice, which lends biological plausibility to the association with childhood leukemia.52

The consistent associations between childhood leukemia and paternal occupation as painters, printers or in motor vehicle related work (e.g., gas station attendants, mechanics, drivers, etc), may be explained by exposure to solvents, although there are other chemicals that might also be involved. For example, people exposed to gasoline and gas exhaust are also exposed to carcinogens such as dichloroethane, dibromomethane and benzo[a]pyrene.53

Other studies are lending weight to the hypothesis that childhood brain cancer is associated with parental solvent exposure, particularly where a father's occupation involves exposure to gasoline, trichloroethylene, methylethylketone or freon.54

The majority of studies summarized in a recent review by Colt and Blair suggest that it is preconceptional and prenatal exposures to organic solvents that carry the greatest relative risks for childhood cancer although some studies have also noted an increased risk with postnatal exposure as well.55 These authors identify that more attention must be paid to adequately assessing the relevant exposure time frame as well as focusing on the influence of maternal exposures to organic solvents.

Pesticides

Experimental studies and in vitro tests have suggested that there are carcinogens represented from all major classes of pesticides including organochlorine and organophosphate insecticides, herbicides, fungicides and fumigants.56 The International Agency for Research on Cancer (IARC) has identified over 45 pesticides as being potential or known carcinogens in animals. Almost half of these are still registered and in common use in the US, including the herbicide atrazine; the insecticides dichlorvos, dicofol and lindane; and the fungicides captan, pentachlorophenol and creosote.57

Epidemiological evidence of pesticides as a risk factor in childhood cancer is variable. Some studies suggest that certain childhood cancers may be related to pesticide exposures either directly or via parental exposure. A large Swedish population-based cohort study indicates increased risk of nervous system tumours, but not leukemia in children whose fathers were exposed to pesticides.58

Additional Swedish research did demonstrate an association between non-Hodgkin's lymphoma (NHL) and exposure to phenoxy herbicides in a case-control study.59 A large retrospective cohort study of Norwegian farm families has determined that there was increased risk of developing certain brain tumours, non-Hodgkins lymphoma, Wilms tumour and other cancers of infancy in farm children, associated with various proxy measures of parental pesticide exposure and use.

Daniels and co-workers conducted a meta-analysis of 31 studies that examined the association between pesticide exposure and incidence of various childhood cancers.61 Despite inadequacies in exposure assessment, these researchers conclude that there is indeed reason to suspect that pre-conceptional, prenatal and early childhood exposures to pesticides are associated with moderate increases in childhood brain tumours and leukemias. Home use of pesticides appeared to account for the greatest risk of these cancers.62 For example, brain cancer was found to be in association with childhood use of lindane for lice treatment.63 Others have suggested that using no-pest strips in the home also increases the risk of childhood brain tumours64 and leukemias.65

Tobacco

There is incontrovertible evidence for the association between ETS and cancer in adults from both toxicological and epidemiological studies. Surprisingly, investigation of the association between pre- and postnatal passive smoking and the incidence of childhood cancer has not yielded similarly definitive findings.

A recent review of roughly 50 relevant epidemiological studies stated that there were only slightly increased relative risks for childhood brain tumours and leukemia-lymphoma with pre- and postnatal passive exposure to ETS.66 These findings, however, are bolstered by toxicological and metabolic data demonstrating damage to DNA in the fetus as well as genotoxic effects in spermatozoa, suggesting that the risk of cancer in childhood from passive exposure to ETS early in life cannot be ignored.67

Infectious Agents

Some propose that polyoma viruses passed on to the fetus transplacentally might explain higher risk for childhood brain cancer, since these viruses can cause DNA mutations. A number of researchers suggest that clusters of childhood leukemia could represent the outcome of unusual epidemics of infectious disease spread by population mixing.68

A similar theory suggests that childhood leukemia occurs when a child with a vulnerable, unchallenged immune system has proliferation of white blood cells from DNA damage caused by a culprit infectious organism. These hypotheses remain speculative despite accumulation of epidemiological research as "no viruses or definitive immunological mechanisms have been identified."69

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