Brain and Other Nervous System continued	Epidemiologic studies have linked nervous system cancers with a variety of environmental exposures, including physical, chemical, and biologic agents (Preston-Martin et al., 1989; Kuijten and Bunin, 1993). Two categories of environmental exposure that have attracted considerable interest in recent years as possible causes of nervous system tumors in humans include electromagnetic fields and a family of chemicals known as N-nitroso compounds. Interest in the latter was prompted by the observation that alkylnitrosoureas, one category of N-nitroso compound, are the most potent neurocarcinogens yet identified in experimental studies with laboratory animals (Kleihues et al., 1976; Magee 1976). Humans are exposed to N-nitroso compounds through a variety of avenues, including diet; use of alcohol and tobacco; certain medications, cosmetics, and lotions; and through their jobs (Preston-Martin and Henderson, 1984). However, results of studies concerning N-nitroso compounds and brain tumors in humans are highly inconsistent (Preston-Martin et al., 1982; Howe et al., 1989; Kuijten et al., 1990; Bunin et al., 1993, 1994a,b; Sarasua and Savitz, 1994). With regard to other dietary factors, some information indicates that consumption of fruits and vegetables and of vitamins C and E might protect against the occurrence of brain tumors (Burch et al., 1987; Bunin et al., 1993). Cancers of the brain and nervous system have been linked to exposure to electromagnetic fields in some studies (Tomenius, 1986; Savitz et al., 1988). Most studies have focused on low-frequency (50-60 Hz) fields, such as those associated with electric power lines and household appliances. There is very little information available concerning possible risks associated with microwave frequencies, such as from hand-held cellular telephones (800-900 MHz). While the possibility of health hazards of EMF exposure remains an active area of research, expert panels that have reviewed the existing evidence have judged that available data are insufficient to support the conclusion that EMF causes cancer (NRPB, 1992). There is strong evidence that high doses of ionizing radiation, such as from radiotherapy, can cause tumors of the nervous system (Ron et al., 1988). The picture is less clear concerning possible risks posed by low doses of radiation. Most studies of occupationally exposed groups have not found an increased risk of brain cancer (Gilbert et al., 1989; Wang et al., 1990; Kendall et al., 1992). Radiation doses associated with diagnostic X-rays are very small and probably pose minimal, if any, risk. Occupational exposures are implicated by the observation that brain cancer occurs more frequently among workers in certain industries: the manufacture of synthetic rubber and polyvinyl chloride, the refining of crude oil and production of petroleum-based chemicals, the manufacture of pharmaceuticals, the nuclear fuels and weapons industry, and farm work that exposes workers to agricultural chemicals (Thomas and Waxweiler, 1986). Certain professional groups, such as anatomists, pathologists, embalmers, chemists, and professional artists, appear to have higher than expected brain cancer rates. Elevated brain cancer rates also have been noted among farmers (Musicco et al., 1988; Blair et al., 1992); precision metal workers; and workers involved in electrical and electronic equipment maintenance, repair and manufacturing (Thomas and Waxweiler, 1986; Thomas et al., 1987). Exposures in these occupations are diverse and include acrylonitrile, vinyl chloride, formaldehyde, lubricating oils, N-nitroso compounds, phenols, pesticides, polycyclic aromatic hydrocarbons, organic solvents, and electromagnetic fields. Many workers are exposed to more than one of these agents, and further, detailed study is required to identify specific causal factors. Although no single substance has yet been directly linked with excess brain cancer risk in humans, a number of chemical compounds have been shown to cause nervous system tumors in experimental animals. Brain tumors have been induced in animals with certain aromatic hydrocarbon compounds, bis-chloromethyl ether, vinyl chloride, and acrylonitrile (Kleihues et al., 1976; Maltoni et al., 1982), as well as with N-nitroso compounds. Studies with experimental animals also suggest that susceptibility to chemical and viral neurocarcinogenesis is greatest during the in utero or early postnatal period of life (Druckrey, 1973). Certain studies have linked elevated brain tumor risk with exposure to farm animals and pets among adults (Choi et al., 1970) and children (Gold et al., 1979), raising speculation about a possible viral etiology. Other possible etiologic factors include severe head trauma and loud noise (for acoustic neuroma) (Schoenberg, 1982). In summary, although a small percentage of cases have been identified as having a genetic or familial component, and studies have linked nervous system cancers with exposure to high-dose ionizing radiation, relatively little is known about the causes of most tumors of the nervous system. It is to be hoped that this will soon change, as results of additional studies become available.
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