Occupational Cancer Research: Current State of Knowledge and Data Gaps

                Occupational cancer has been an active field of research for many decades. Cancer is somewhat unique in that it has a well-accepted international classification system for causes established by the International Agency for Research on Cancer (IARC), compared to other occupational diseases that are less well defined. Currently there are approximately 60 definite (Category 1) or probable (Category 2A) workplace carcinogens, as defined by IARC.   These include many common workplace agents hundreds of thousands or workers are regularly exposed to, including industrial chemicals (e.g. benzene, formaldehyde, 1,3-butadiene, ethylene oxide, PCBs and dioxins), metals (e.g. chromium, arsenic, nickel, beryllium, and cadmium), fibres (e.g. asbestos and erionite), particulates  (e.g. crystalline silica, wood dust, and leather dust),  ionizing radiation (including x-rays, gamma, radon decay products, and plutonium), UV solar radiation, polycyclic aromatic hydrocarbon-related exposures (e.g. unrefined mineral oils and creosote), products of combustion (e.g. soot, coal tar pitch volatiles, environmental tobacco smoke and diesel exhaust), and  many exposure circumstances that are classified as known or suspected carcinogens, such as shiftwork involving light at night and employment as a painter or welder.

The WHO has estimated that there are 152,000 occupational lung and blood cancer deaths annually:102,000 lung cancers, 43,000 mesotheliomas, and 7,000 cases of leukemia. These data have been instrumental in raising awareness about occupational mortality but they are only based on exposure to 11 carcinogens, extrapolated from the European CAREX project, with just these three cancer sites. The best national efforts to estimate the burden of occupational carcinogens have predicted much greater numbers (in terms of the proportion of all cancer), but have used country-specific exposure data for dozens of carcinogens and many more cancer sites. The major limitation for these projects is the availability of population-level exposure information. In recent years a number of national exposure databases have been created and more exposure surveillance projects, such as CAREX Canada, have been launched, but more national exposure projects are needed. These types of projects are not only helpful for assessing burden, they also provide essential data for planning and setting prevention priorities and for targeting regulatory efforts. 

                Many of the over 100 workplace exposures classified as possible carcinogens by IARC (Category 2B)  are very common. As with the established carcinogens, this is also a very diverse set of substances including pesticides (e.g. 2,4-D, MCPA, MCPP, chlorothalonil, dichlorvos, chlordane, lindane, and pentachlorophenol), chlorinated solvents (e.g. carbon tetrachloride, 1,2-dichloroethane, dichloromethane, and chloroform), metals (e.g. antimony trioxide, vanadian pentoxide, and cobalt), industrial chemicals (e.g. ethylbezene, naphthalene, di(2-ethylhexyl) phthalate (DEHP), styrene, and acrylonitrile)  and some substances formerly thought to be inert (e.g. titanium dioxide and carbon black). Beyond those that have already been classified as possible human carcinogens there are many other workplace exposures with at least some suspicion of human carcinogenicity (IARC Category 3) and more that have received little or no formal evaluation.

Despite the industrious work of occupational cancer researchers over last hundred years, the task before them remains large. Reports have been released in the past few years proposing priority listings of substances to be evaluated by IARC or targeted for more research. In 2008, IARC released a report of the Advisory Group to Recommend Priorities for Evaluation as part of the IARC Monographs Program. This list included a number of the agents that had previously been classified by IARC as 2A and 2B carcinogens, such trichloroethylene and other chlorinated solvents, styrene, PCBs, polybrominated biphenyls, DEHP and other phthalates, bitumens, radio frequency electromagnetic fields, atrazine, vehicle exhausts, and welding.  It also includes some relatively new issues such as carbon-based nanoparticles, perfluorinated compounds (e.g. PFOA), and crystalline fibres other than asbestos, as well as non-traditional issues for occupational cancer research, such as sedentary work and stress. An international committee of researchers chosen by the American Cancer Society, IARC and the U.S. National Institute for Occupational Safety and Health recently produced a report on Research Recommendations for Selected IARC-classified Agents. As might be expected, there is an overlap with the substances on the IARC priority list (e.g. styrene, PCBs, DEHP). Exposures that occur in the form of fine and ultra-fine particles are recommended, such as titanium dioxide, carbon black, diesel engine exhaust, and welding fumes. There are also a number of chlorinated solvents (e.g. trichloroethylene, perchloroethylene, methylene chloride, and chloroform) and metals (e,g, lead and lead compounds, indium phosphide, and metallic cobalt). Shiftwork and formaldehyde, both recently reviewed by IARC, are also on the list because of unresolved issues. Atrazine is the only pesticide listed. 

                These priorities overlap well with the research priorities that the labour, industry, and government stakeholders of my Centre have identified, however, there are a number of other substances of particular relevance to Canada. For example, there are many pesticides that remain in IARC Category 2B and, in Canada alone, hundreds of thousands of agricultural workers are exposed to these substances. Research must target the carcinogenicity of these pesticides, so that farmers can chose the least toxic alternatives. A number of common pharmaceuticals, particularly anti-neoplastic agents, are known to cause cancer but it is unclear whether health care workers are at increased risk. A very high risk of sinonasal adenocarcinoma has been observed among workers with high exposure to wood dust but the carcinogenicity of specific tree species is not known. There are a very large number of commonly used substances that have never been evaluated; identification of new carcinogens should also be a priority. 

                Occupational cancer research faces many challenges. Our research is not seen as a priority for most funding agencies, for example, a recent survey of cancer research funding in Canada found that only 0.1% of all cancer research funding is directed towards occupational cancer and the situation is similar in other countries. It is becoming increasingly difficult to conduct retrospective cohort studies, traditionally the “workhorse” of occupational cancer, due to lack of cooperation from many employers and increasingly strict privacy legislation. Although national and international workplace exposure projects have been developed and methods for using exposure data are improving, acquiring adequate exposure data for studies remains difficult. Very few countries have occupational cancer surveillance programs that could be used to inexpensively evaluate new hypotheses or monitor cancer risk in potentially exposed populations. We will need to overcome these difficulties, attract new researchers to the field of occupational cancer and communicate the continued importance of occupational cancer to our stakeholders if we are to have the capacity to meet these challenges.