Scandinavian Journal of Work, Environment & Health (Nov 2022)
What is next for occupational cancer epidemiology?
Abstract
Research on occupational causes of cancer has identified 47 known (Group 1) agents associated with 23 types of cancer through 2017, an increase from 28 agents in 2004 (1, 2). Occupational agents include chemicals and chemical mixtures; radiation and radionuclides; airborne particles and complex mixtures; and metals and metal compounds. The global burden of cancer due to 14 of the Group 1 agents was estimated to total 349 000 [95% uncertainty interval (UI) 269 000–427 000] deaths in 2016, or 3.9% (95% UI 3.2–4.6%) of all cancer deaths, including 299 998 or 17.6% (95% UI 13.8–21.3%) of lung cancer deaths (3). There are also exposures in various occupations, industries, or processes classified as Group 1 where the causal agent is not necessarily identified. In 2022, occupational exposure as a firefighter was most recently classified in Group 1, with sufficient evidence among humans for mesothelioma and bladder cancer, and limited evidence for other cancers (4). Despite achievements in identifying occupational causes of cancer, a range of research needs remain, including identifying additional cancer sites for Group 1 agents and more definitive studies for exposures where the evidence among humans remains limited or inadequate (1, 5–7). There may be outstanding methodological concerns or findings that are inconsistent or of poor quality or informativeness. Research recommendations to address classification uncertainties for 20 priority occupational agents have been detailed (8). They include conducting new epidemiological studies in highly exposed occupations or populations, improving (quantitative) exposure assessment including through biomarkers of exposure, enhancing statistical power through extended follow-up or pooled studies, and furthering human mechanistic studies. High quality human mechanistic evidence can provide valuable information when epidemiology studies are not available or feasible (5). A 2019 Advisory Group considered 170 different agents in terms of their suitability for (re-)evaluation with a range of chemical, metal, or complex exposures of relevance for occupational settings prioritized based on new human epidemiology, mechanistic and/or cancer bioassay data (9). There have been calls to update existing cohorts when valuable follow-up time has accrued allowing investigation of the full potential impact of exposures on health (10). There is a longstanding need for occupational epidemiological and exposure assessment studies in low- and middle-income countries, where there are often few or no available studies and exposure levels maybe higher (11–14). There may also be differences in working conditions, exposure patterns, and worker protections (15, 16). Research challenges include declines in participation rates, funding, and research infrastructures (1, 17–19). In parallel, epidemiological research has innovated over time to comprise increasingly larger-scale prospective cohort studies and consortia, use of electronic data linkage, causal inference methods and triangulation of evidence, reinforcing the ongoing utility of observational research methods (20). The recent COVID-19 pandemic has reinforced the need for a global perspective in epidemiological research, multidisciplinarity, and broadening perspectives regarding fundamental underlying determinants of health (21, 22). There have also been calls for greater equity and inclusiveness in health research, both in Europe, and worldwide (23, 24). Efforts to stimulate future research and investment in occupation and cancer may benefit from the use of new rapidly evolving research methods, closer alignment with global public health priorities, and strengthening of international partnerships supporting excellence and inclusiveness in research. For example, a range of methodological advancements have emerged from application of exposome concepts in epidemiology. In Europe, birth cohort consortia seeking to characterize the early-life exposome, as well as other efforts, have driven much innovation (25, 26). The exposome concept was proposed in 2005 to stimulate investment to better characterize environmental exposures throughout the lifecourse using novel technologies, offering a complementary perspective to that of the genome (27). Although occupational exposure has previously not been emphasized, research in the internal and external occupational exposome is now beginning to emerge (28). A range of statistical methods for analysis of multiple correlated exposures have advanced (29). Extended Bayesian profile regression mixture (PRM) models have been used to examine multiple highly correlated ionizing radiation exposures for lung cancer risk among miners (30). An exposome-wide association study examined a range of personal and occupational factors in B-cell lymphoma, suggesting that single-factor research approaches maybe suboptimal for new disease insights (31). There are exposome technologies for personal monitoring of workers (28, 32) and other novel research methods including natural language processing and text mining (33, 34), automated network assembly approaches to summarizing literature (35), efforts to combine epidemiological data with those from other evidence streams (36), and new technologies to facilitate secure decentralized pooled analyses of data (37). However, there is an ongoing need for continued efforts to better characterize the occupational and corresponding non-occupational exposome over the lifecourse. Research priorities include establishing new cohort studies with appropriate biosample collection, improved questionnaire and personal monitoring data, increasing multidisciplinary collaboration to utilize innovative data and methods, and integrating genetic data in exposome studies for causal inference (38-40). At the same time, careful consideration of the policy relevance of exposome studies remains of importance (41), as are continued efforts in conventional epidemiological case–control and cohort studies in occupation and cancer (8). Occupational studies examining exposures of relevance for the general population may favor greater investment (42). There are environmental exposure routes for occupational agents, bystander or spousal exposure to occupational agents, and potential transgenerational health effects (43–45). Birth cohorts may represent a typically underused resource for research in occupation and health (46). Principles for safeguarding integrity in environmental and occupational research have also been outlined (47). Research on occupation and cancer may benefit from closer alignment with recent high-profile initiatives on related topics as well as with global public health priorities. The United Nations Sustainable Development Goals note the need for decent work (48). The EU Strategic Framework on Health and Safety at Work describes the elimination of work-related deaths by 2030 and reduced illness through improved data collection, updated rules on hazardous substances, including those of relevance for renewable energy technologies (ie, lead, cobalt) or of asbestos exposure in building renovations for greening, increased health literacy at work, and adapting working conditions for patients (49). A large-scale survey of worker exposure to cancer risk factors is being implemented in Europe to collect standardized data across different European countries (50). The Health Environment Agenda for Europe project defined priority areas for research on rapidly changing work and employment conditions, climate change and worker health, working time and long working hours, ageing workers, and neglected work-related diseases (51). Rapidly changing work conditions were exemplified during the COVID-19 pandemic, with potential direct or indirect effects on health and cancer. Shifts in overall global cancer research focus were also described (52). Increasing unemployment and economic downturns in high- and middle-income countries have been associated with increased cancer mortality for treatable cancers, with less access to healthcare underlying findings (53). There is also increasing interest in precarious employment and potential direct or indirect impacts on health and quality of life (54). Public health efforts directed at catching-up in cancer screening and on improving health systems and public health literacy following the COVID-19 pandemic may offer opportunities to advance cancer control and improved health literacy at work (55, 56). Further, there may greater opportunities for strengthened clinical partnerships for occupational epidemiologists. For example, dramatic gains in survival due to early detection have been demonstrated for lung cancer (57). However, occupational (or environmental) exposures are not systematically incorporated into screening algorithms, and further research and collaboration with clinical partners is warranted (58–61). The potential importance of climate change in cancer, including occupation and cancer, may also not be fully understood (62, 63). Climate change may relate to increasing exposure to environmental or occupational carcinogens, including air pollution, adverse dietary exposures, changes in physical activity levels, ultraviolet radiation, water pollution, infections, and parasites due to extreme weather events, wildfires (4), heat, sea-level rise, and changes in land-use. There may also be disruptions in cancer care. Climate change may further exacerbate existing socioeconomic inequities, and social determinants of cancer. Increasing occupational heat stress is related to acute and chronic health effects as well as reduced productivity (64–66). Studies of occupational heat exposure and cancer risk are beginning to emerge (67). Interventions to jointly address climate change and disease prevention, including cancer, have been proposed (68). There are also new agents rapidly entering the workplace where little is known regarding their carcinogenicity to humans. A planetary health perspective suggests that humanity is outside the safe operating space of the planetary boundary, with increasing production and release of chemical industry production exceeding the ability to conduct safety assessments (69). Lastly, strengthened international partnerships are critical for future advances in occupational cancer research. Efforts in coordination of European birth cohort studies, and later occupational cohort studies, have led to major advancements in research and inclusiveness (25, 26, 70, 71). Network funding initiatives provide valuable support and developed out of a recognized need to increase equitable access to funding and research infrastructures (72). A recent example is the OMEGA-NET COST Action, which sought to improve coordination and harmonization of European occupational cohort studies by connecting researchers through a range of research coordination and capacity building activities, with a particular focus on connecting researchers in traditionally less research-intensive countries (71). Online inventories of occupational cohort studies and exposure assessment tools were developed (73, 74) as were advancements in theoretical frameworks, consensus definitions and recommendations for future research on emerging topics in occupational health (54, 75, 76). The need for occupational epidemiological and exposure monitoring studies in low- and middle-income countries has long been recognized. Priorities for cancer research in low- and middle-income countries have recently been described as separate to those of high-income countries, and highlighted the need to reduce the burden of patients presenting with advanced-stage disease, primary prevention and early detection, and innovative and affordable technology in cancer control (77). Documenting and minimizing exposure to established occupational carcinogens is critical to prioritize interventions and prevent future cancer burden (11, 34, 78). Generating country-specific evidence for effective prevention may be helpful in this regard (77). Research questions on cancers that are of local importance, using appropriate research methods for available infrastructure, and partnerships for mutually rewarding collaborations have been described (77, 79). However, cancer registry and infrastructure challenges have been outlined, including of poor-quality data and an absence of legal frameworks for cancer registration (19). International collaboration has had demonstrated impacts in research and capacity building, though sustained political and financial commitment is needed (16, 80, 81). The occupational epidemiology community has a great opportunity to promote new efforts in occupation and cancer while at the same time reducing inequalities in health and research. Acknowledgements Michelle C Turner is funded by a Ramón y Cajal fellowship (RYC-2017-01892) from the Spanish Ministry of Science, Innovation and Universities and co-funded by the European Social Fund. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. References 1. Loomis D, Guha N, Hall AL, Straif K. Identifying occupational carcinogens: an update from the IARC Monographs. Occup Environ Med 2018;75:593-603. https://doi.org/10.1136/oemed-2017-104944 2. 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