Magnitude of the Problem
The first clear-cut evidence of cancer causation involved an occupational carcinogen (Checkoway, Pearce and Crawford-Brown 1989). Pott (1775) identified soot as the cause of scrotal cancer in London chimney-sweeps, and graphically described the abysmal working conditions, which involved children climbing up narrow chimneys that were still hot. Despite this evidence, reports of the need to prevent fires in chimneys were used to delay legislation on child labour in this industry until 1840 (Waldron 1983). An experimental model of soot carcinogenesis was first demonstrated in the 1920s (Decoufle 1982), 150 years after the original epidemiological observation.
In subsequent years, a number of other occupational causes of cancer have been demonstrated through epidemiological studies (although the association with cancer has usually first been noted by occupational physicians or by workers). These include arsenic, asbestos, benzene, cadmium, chromium, nickel and vinyl chloride. Such occupational carcinogens are very important in public health terms because of the potential for prevention through regulation and improvements in industrial hygiene practices (Pearce and Matos 1994). In most instances, these are hazards which markedly increase the relative risk of a particular type or types of cancer. It is possible that other occupational carcinogens remain undetected because they involve only a small increase in risk or because they simply have not been studied (Doll and Peto 1981). Some key facts about occupational cancer are given in table 1.
Table 1. Occupational cancer: Key facts.
- Some 20 agents and mixtures are established occupational carcinogens; a similar number of chemicals are highly suspected occupational carcinogens.
- In industrialized countries, occupation is causally linked to 2 to 8% of all cancers; among exposed workers, however, this proportion is higher.
- No reliable estimates are available on either the burden of occupational cancer or the extent of workplace exposure to carcinogens in developing countries.
- The relatively low overall burden of occupational cancer in industrialized countries is the result of strict regulations on several known carcinogens; exposure to other known or highly suspected agents, however, is still allowed.
- Although several occupational cancers are listed as occupational diseases in many countries, a very small fraction of cases is actually recognized and compensated.
- Occupational cancer is-to a very large extent-a preventable disease.
Occupational causes of cancer have received considerable emphasis in epidemiological studies in the past. However, there has been much controversy regarding the proportion of cancers which are attributable to occupational exposures, with estimates ranging from 4 to 40% (Higginson 1969; Higginson and Muir 1976; Wynder and Gori 1977; Higginson and Muir 1979; Doll and Peto 1981; Hogan and Hoel 1981; Vineis and Simonato 1991; Aitio and Kauppinen 1991). The attributable cancer risk is the total cancer experience in a population that would not have occurred if the effects associated with the occupational exposures of concern were absent. It may be estimated for the exposed population, as well as for a broader population. A summary of existing estimates is shown in table 2. Universal application of the International Classification of Diseases is what makes such tabulations possible (see box).
Table 2. Estimated proportions of cancer (PAR) attributable to occupations in selected studies.
|Study||Population||PAR and cancer site||Comments|
|Higginson 1969||Not stated||1% Oral cancer
1-2% Lung cancer
10% Bladder cancer
2% Skin cancer
|No detailed presentation of exposure levels and other assumptions|
|Higginson and Muir 1976||Not stated||1-3% Total cancer||No detailed presentation of assumptions|
|Wynder and Gori 1977||Not stated||4% Total cancer in men,
2% for women
|Based on one PAR for bladder cancer and two personal communications|
|Higginson and Muir 1979||West Midland, United Kingdom||6% Total cancer in men,
2% total cancer
|Based on 10% of non-tobacco related lung cancer, mesothelioma, bladder cancer (30%), and leukaemia in women (30%)|
|Doll and Peto 1981||United States early 1980||4% (range 2-8%)
|Based on all studied cancer sites; reported as ‘tentative’ estimate|
|Hogan and Hoel 1981||United States||3% (range 1.4-4%)
|Risk associated with occupational asbestos exposure|
|Vineis and Simonato 1991||Various||1-5% Lung cancer,
16-24% bladder cancer
|Calculations on the basis of data from case-control studies. Percentage for lung cancer considers only exposure to asbestos. In a study with a high proportion of subjects exposed to ionising radiation, a 40% PAR was estimated. Estimates of PAR in a few studies on bladder cancer were between 0 and 3%.|
The International Classification of Diseases
Human diseases are classified according to the International Classification of Diseases (ICD), a system that was started in 1893 and is regularly updated under the coordination of the World Health Organization. The ICD is used in almost all countries for tasks such as death certification, cancer registration and hospital discharge diagnosis. The Tenth Revision (ICD-10), which was approved in 1989 (World Health Organization 1992), differs considerably from the previous three revisions, which are similar to each other and have been in use since the 1950s. It is therefore likely that the Ninth Revision (ICD-9, World Health Organization 1978), or even earlier revisions, will still be used in many countries during the coming years.
The large variability in the estimates arises from the differences in the data sets used and the assumptions applied. Most of the published estimates on the fraction of cancers attributed to occupational risk factors are based on rather simplified assumptions. Furthermore, although cancer is relatively less common in developing countries due to the younger age structure (Pisani and Parkin 1994), the proportion of cancers due to occupation may be higher in developing countries due to the relatively high exposures which are encountered (Kogevinas, Boffetta and Pearce 1994).
The most generally accepted estimates of cancers attributable to occupations are those presented in a detailed review on the causes of cancer in the population of the United States in 1980 (Doll and Peto 1981). Doll and Peto concluded that about 4% of all the deaths due to cancer may be caused by occupational carcinogens within “acceptable limits” (i.e., still plausible in view of all the evidence at hand) of 2 and 8%. These estimates being proportions, they are dependent on how causes other than occupational exposures contribute to produce cancers. For example, the proportion would be higher in a population of lifetime non-smokers (such as the Seventh-Day Adventists) and lower in a population in which, say, 90% are smokers. Also the estimates do not apply uniformly to both sexes or to different social classes. Furthermore, if one considers not the whole population (to which the estimates refer), but the segments of the adult population in which exposure to occupational carcinogens almost exclusively occurs (manual workers in mining, agriculture and industry, broadly taken, who in the United States numbered 31 million out of a population, aged 20 and over, of 158 million in the late 1980s), the proportion of 4% in the overall population would increase to about 20% among those exposed.
Vineis and Simonato (1991) provided estimates on the number of cases of lung and bladder cancer attributable to occupation. Their estimates were derived from a detailed review of case-control studies, and demonstrate that in specific populations located in industrial areas, the proportion of lung cancer or bladder cancer from occupational exposures may be as high as 40% (these estimates being dependent not only on the local prevailing exposures, but also to some extent on the method of defining and assessing exposure).
Mechanisms and Theories of Carcinogenesis
Studies of occupational cancer are complicated because there are no “complete” carcinogens; that is, occupational exposures increase the risk of developing cancer, but this future development of cancer is by no means certain. Furthermore, it may take 20 to 30 years (and at least five years) between an occupational exposure and the subsequent induction of cancer; it may also take several more years for cancer to become clinically detectable and for death to occur (Moolgavkar et al. 1993). This situation, which also applies to non-occupational carcinogens, is consistent with current theories of cancer causation.
Several mathematical models of cancer causation have been proposed (e.g., Armitage and Doll 1961), but the model which is simplest and most consistent with current biological knowledge is that of Moolgavkar (1978). This assumes that a healthy stem cell occasionally mutates (initiation); if a particular exposure encourages the proliferation of intermediate cells (promotion) then it becomes more likely that at least one cell will undergo one or more further mutations producing a malignant cancer (progression) (Ennever 1993).
Thus, occupational exposures can increase the risk of developing cancer either by causing mutations in DNA or by various “epigenetic” mechanisms of promotion (those not involving damage to DNA), including increased cell proliferation. Most occupational carcinogens which have been discovered to date are mutagens, and therefore appear to be cancer initiators. This explains the long “latency” period which is required for further mutations to occur; in many instances the necessary further mutations may never occur, and cancer may never develop.
In recent years, there has been increasing interest in occupational exposures (e.g., benzene, arsenic, phenoxy herbicides) which do not appear to be mutagens, but which may act as promoters. Promotion may occur relatively late in the carcinogenic process, and the latency period for promoters may therefore be shorter than for initiators. However, the epidemiological evidence for cancer promotion remains very limited at this time (Frumkin and Levy 1988).
Transfer of Hazards
A major concern in recent decades has been the problem of the transfer of hazardous industries to the developing world (Jeyaratnam 1994). Such transfers have occurred in part due to the stringent regulation of carcinogens and increasing labour costs in the industrialized world, and in part from low wages, unemployment and the push for industrialization in the developing world. For example, Canada now exports about half of its asbestos to the developing world, and a number of asbestos-based industries have been transferred to developing countries such as Brazil, India, Pakistan, Indonesia and South Korea (Jeyaratnam 1994). These problems are further compounded by the magnitude of the informal sector, the large numbers of workers who have little support from unions and other worker organizations, the insecure status of workers, the lack of legislative protection and/or the poor enforcement of such protection, the decreasing national control over resources, and the impact of the third world debt and associated structural adjustment programmes (Pearce et al. 1994).
As a result, it cannot be said that the problem of occupational cancer has been reduced in recent years, since in many instances the exposure has simply been transferred from the industrialized to the developing world. In some instances, the total occupational exposure has increased. Nevertheless, the recent history of occupational cancer prevention in industrialized countries has shown that it is possible to use substitutes for carcinogenic compounds in industrial processes without leading industry to ruin, and similar successes would be possible in developing countries if adequate regulation and control of occupational carcinogens were in place.
Prevention of Occupational Cancer
Swerdlow (1990) outlined a series of options for the prevention of exposure to occupational causes of cancer. The most successful form of prevention is to avoid the use of recognized human carcinogens in the workplace. This has rarely been an option in industrialized countries, since most occupational carcinogens have been identified by epidemiological studies of populations that were already occupationally exposed. However, at least in theory, developing countries could learn from the experience of industrialized countries and prevent the introduction of chemicals and production processes that have been found to be hazardous to the health of workers.
The next best option for avoiding exposure to established carcinogens is their removal once their carcinogenicity has been established or suspected. Examples include the closure of plants making the bladder carcinogens 2-naphthylamine and benzidine in the United Kingdom (Anon 1965), termination of British gas manufacture involving coal carbonization, closure of Japanese and British mustard gas factories after the end of the Second World War (Swerdlow 1990) and gradual elimination of the use of benzene in the shoe industry in Istanbul (Aksoy 1985).
In many instances, however, complete removal of a carcinogen (without closing down the industry) is either not possible (because alternative agents are not available) or is judged politically or economically unacceptable. Exposure levels must therefore be reduced by changing production processes and through industrial hygiene practices. For example, exposures to recognized carcinogens such as asbestos, nickel, arsenic, benzene, pesticides and ionizing radiation have been progressively reduced in industrialized countries in recent years (Pearce and Matos 1994).
A related approach is to reduce or eliminate the activities that involve the heaviest exposures. For example, after an 1840 act was passed in England and Wales prohibiting chimney-sweeps from being sent up chimneys, the number of cases of scrotal cancer decreased (Waldron 1983). Exposure also can be minimized through the use of protective equipment, such as masks and protective clothing, or by imposing more stringent industrial hygiene measures.
An effective overall strategy in the control and prevention of exposure to occupational carcinogens generally involves a combination of approaches. One successful example is a Finnish registry which has as its objectives to increase awareness about carcinogens, to evaluate exposure at individual workplaces and to stimulate preventive measures (Kerva and Partanen 1981). It contains information on both workplaces and exposed workers, and all employers are required to maintain and update their files and to supply information to the registry. The system appears to have been at least partially successful in decreasing carcinogenic exposures in the workplace (Ahlo, Kauppinen and Sundquist 1988).