Occupational exposure and cancer: an umbrella review

Raphael Mendonça Guimarães Viviane Gomes Parreira Dutra Andréia Rodrigues Gonçalves Ayres Helena Beatriz da Rocha Garbin Thalyta Cássia de Freitas Martins Karina Cardoso Meira About the authors

Resumo

Objetivo:

fornecer uma visão geral das associações entre exposição ocupacional e risco da ocorrência ou morte por câncer.

Métodos:

esta revisão guarda-chuva da literatura utilizou as bases Medline e Web of Science. A partir de protocolo de busca, foram incluídas metanálises para diversas circunstâncias ocupacionais e cânceres selecionados que possuíssem algum nível de evidência para associação com ocupação.

Resultados:

foram incluídas 37 metanálises, abrangendo 18 localizações de câncer. Considerando a avaliação da heterogeneidade dos estudos, da qualidade da evidência e da força de associação, obteve-se evidências altamente sugestivas de associações entre exposição a solvente e mieloma múltiplo; amianto e câncer de pulmão; hidrocarbonetos e câncer de trato aerodigestivo superior; e estresse ocupacional e câncer colorretal.

Conclusão:

há evidências robustas para associar exposições ocupacionais e tipos de câncer não previstos, inicialmente, nas orientações de vigilância do câncer relacionado ao trabalho no Brasil. Permanecem lacunas sobre exposições de grande relevância, que carecem de metanálises mais consistentes, por exemplo, exposição a poeiras inorgânicas e câncer de pulmão e mesotelioma; exposição a solventes e tumores hematológicos. Evidências de câncer em outras regiões anatômicas foram menos robustas, apresentando indícios de incerteza ou viés.

Palavras-Chave:
exposição ocupacional; câncer; câncer ocupacional, saúde do trabalhador

Abstract

Objective:

to provide an overview of the associations between occupational exposure and risk of occurrence or death from cancer.

Methods:

this umbrella review used the Medline and Web of Science databases. Based on the search protocol, meta-analysis was included for several occupational circumstances and selected cancers that had some level of evidence associated with the occupation.

Results:

37 meta-analysis were included, covering 18 cancer locations. By assessing the heterogeneity of studies, quality of evidence, and strength of association, results highly indicated associations between solvent exposure and multiple myeloma, asbestos and lung cancer, hydrocarbons and upper aerodigestive tract cancer, occupational stress and colorectal cancer.

Conclusion:

robust evidence shows an association between occupational exposures and types of cancer not initially foreseen in the guidelines for work-related cancer surveillance in Brazil. Gaps in relevant exposures require further research and more consistent meta-analysis, including: exposure to inorganic dust and lung cancer and mesothelioma; solvents and hematological tumors. Evidence of cancer in other anatomical regions was less robust, showing signs of uncertainty or bias.

Keywords:
occupational exposure; cancer; occupational cancer, occupational health

Introduction

Cancer is the first or second leading cause of premature death (deaths between 30 and 69 years old) in 73% of countries worldwide. In 2016, 29.8% of deaths from non-communicable diseases were caused by cancer11. Wild CP, Weiderpass E, Stewart BW, editors. World Cancer Report: Cancer research for cancer prevention. Lyon: IARC; 2020.. In Brazil, the estimated incidence of this disease for the 2020-2022 triennium indicates more than 625,000 new cases per year22. Instituto Nacional de Câncer (BR). Estimativa 2020: incidência de câncer no Brasil. Rio de Janeiro: INCA; 2019..

Current scientific evidence supports the association between work and some types of cancer33. Hashim D, Boffetta P. Occupational and environmental exposures and cancers in developing countries. Ann Glob Health. 2014;80(5):393-411.), (44. Boffetta P. Human cancer from environmental pollutants: the epidemiological evidence. Mutat. Res Genet Toxicol Environ Mutagen. 2006;608(2):157-62.), (55. Clapp RW, Howe GK, Jacobs MM. Environmental and occupational causes of cancer: a call to act on what we know. Biomed Pharmacother. 2007;61(10):631-9.. In fact, the World Health Organization estimates that about 19% of all cancers are attributed to the environment, including work environments66. World Health Organization. Prevention of occupational cancer. The Global Occupational Health Network (GOHNET) Newsletter. 2006;(11).. Occupational exposure is the main route of human exposure to about half of the chemicals and mixtures classified by the International Agency for Research on Cancer (IARC) as carcinogenic to humans77. Cogliano VJ, Baan R, Straif K, Grosse Y, Lauby-Secretan B, El Ghissassi F, Bouvard V, et al. Preventable exposures associated with human cancers. J Natl Cancer Inst. 2011;103(24):1827-39.), (88. Clapp RW, Jacobs MM, Loechler EL. Environmental and Occupational Causes of Cancer New Evidence, 2005-2007. Rev Environ Health. 2008;23(1):1-37..

In Brazil, work-related cancers have been poorly estimated. National evidence and registration are insufficient because of the under-registration of cases and the invisibility of the location of cancers recognized by the Brazilian surveillance system99. Instituto Nacional de Câncer (BR). Coordenação Geral de Ações Estratégicas. Coordenação de Prevenção e Vigilância. Área de Vigilância do Câncer relacionado ao Trabalho e ao Ambiente. Diretrizes para a vigilância do câncer relacionado ao trabalho; organizadora Fátima Sueli Neto Ribeiro. Rio de Janeiro: INCA; 2012.. Initially, according to the definition of work-related cancer from the Information System for Notifiable Diseases (SINAN), sentinel events would be cases of leukemia caused by benzene exposure, asbestos mesothelioma, and liver angiosarcoma by exposure to vinyl chloride, among others1010. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância em Saúde Ambiental e do Trabalhador. DRT - Câncer Relacionado ao Trabalho, instruções para preenchimento. Brasília, DF; 2005.. More recently, the Ministry of Health began considering these events as “all cases of cancer caused by exposure to factors, agents, and risk situations in the work environment and process, even after the exposure has ceased” (p.2) (1111. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Saúde Ambiental, do Trabalhador e Vigilância das Emergências em Saúde Pública. Nota Informativa Nº 94/2019-DSASTE/SVS/MS. Orientação sobre as novas definições dos agravos e doenças relacionados ao trabalho do Sistema de Informação de Agravos de Notificação (Sinan). Brasília, DF; 2019..

Several new epidemiological studies are conducted and published annually to examine if occupational exposure increases the risk of developing other types of cancer. The global burden of disease for work-related kidney, breast, nasopharynx, larynx, lung, mesothelioma, ovary, and leukemia cancers was recently estimated1212. Global Burden of Disease 2016 Occupational Carcinogens Collaborators. Occupational Carcinogens Collaborators. Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016. Occup Environ Med. 2020;77(3):151-9.. However, prospective cohort studies and meta-analysis show that occupational exposures are also associated with cancers in other locations, such as the central nervous system, prostate, nasal cavity, esophagus, bladder, liver, and bile ducts1313. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância em Saúde Ambiental e Saúde do Trabalhador. Atlas do Câncer Relacionado ao Trabalho no Brasil. Brasília, DF; 2018.. Assuming these associations are causative, a significant burden of cancer could be avoided since occupational exposures are largely preventable1414. Purdue MP, Hutchings SJ, Rushton L, Silverman DT. The proportion of cancer attributable to occupational exposures. Ann Epidemiol. 2015;25(3):188-92..

For more than half a century, IARC has classified agents, combinations of agents, and exposure circumstances according to carcinogenicity/threat to humans in their monographs. Among the assessed items, classified as “definitely”, “probably”, or “possibly” carcinogenic, many are related to work1515. International Agency for Research Cancer [homepage na internet]. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans [citado em 13 mai 2021]. Disponível em: https://monographs.iarc.who.int/.
https://monographs.iarc.who.int/...
.

Seeking to contribute to evidence-based decision-making, this study aims to overview the associations between occupational exposure and cancer development or death risk. Studies that show positive results and statistically significant associations are more likely to be published than those with negative findings with no statistical significance, thus misguiding clinical and public health decisions1616. Dwan K, Gamble C, Williamson PR, Kirkham JJ. Systematic review of the empirical evidence of study publication bias and outcome reporting bias - an updated review. PLoS One. 2013;8(7):e66844.. Moreover, biases in the literature explain the effect indicated by state of the art.

Methods

To summarize and assess the existing evidence and its quality, a comprehensive umbrella review was conducted with meta-analysis that investigated the association between occupational exposure and risk of cancer occurrence or death1717. Fusar-Poli P, Radua J. Ten simple rules for conducting umbrella reviews. Evid Based Ment Health. 2018;21(3):95-100..

Research question

The PECOS strategy was used, considering: adult workers aged 18 years or older (P = population) assessed for occupational exposure to carcinogens (E = exposure) and compared with non-exposed workers (C = comparison of exposures or control) to verify the association with the development of work-related cancer (O = outcome) in systematic reviews and meta-analysis (S = studies), resulting in the following guide question: “What cancers are most associated with occupational exposure?”.

Eligibility criteria

Meta-analysis on the association between occupational exposure and cancer risk was eligible. No restrictions were established regarding the type or year of publication. Eligibility was restricted to English, Spanish, French, and Portuguese publications. Studies conducted in population groups of non-workers and people with children were excluded.

Information sources and search strategies

Searches were conducted in Medline and Web of Science databases for systematic reviews and meta-analysis published until March 2020 to investigate the association between occupational exposures and cancer risk. Initially, the agreement between the different bases was verified. Since it surpassed 90%, the search was conducted from the most comprehensive basis, Medline, using the following terms: (occupational OR work-related) AND (cancer OR neoplasm OR tumor) AND (risk factor OR attributable risk) AND (exposure) AND (systematic review OR meta-analysis).

Review selection and assessment of methodological quality

After excluding duplicates, two researchers (Ayres and Garbin) independently selected eligible systematic reviews and meta-analysis from their titles and abstracts. The articles chosen initially were submitted for duplication check. The eligibility data were stored by double data entry. The disagreements between the evaluators regarding eligibility were resolved by a third researcher (Dutra).

At the end of this stage, the selected articles were read in full to verify if they met the PECOS criteria. In the next step, the quality of the remaining articles was verified. The methodological quality assessment of systematic reviews and meta-analysis included was conducted independently using the AMSTAR-2 (Assessment of Multiple Systematic Reviews) instrument1818. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008..

Different criteria measured agreement between the researchers: i) agreement on article classification, attributed by AMSTAR-2 (critical quality; low quality; moderate quality; and high quality) and measured by weighted kappa; ii) item-to-item agreement, assessed by simple kappa; iii) 16 assessment items of AMSTAR-2. These criteria are weighted differently according to the degree of relevance of the domains evaluated (e.g., quality of statistical measures, information on publication bias, etc.). To obtain a simple agreement measure for the articles, a general score was created from the simple sum of the items. The Altman-Bland plot assessed the agreement of this score.

Data collection

A data collection form was developed. The first stage included data on the type of study, research group, year of publication, journal, type of cancer, type of exposure, epidemiological measure (Mortality, incidence, prevalence), and search strategy (descriptors).

Information was obtained on types of studies included (cross-sectional, case-control, and cohort), the number of studies, variables of the quality assessment instrument (AMSTAR-2), heterogeneity (yes, no, or not applicable), a summary measure of association (with a respective confidence interval of 95%), summary measure for random effects (with a respective confidence interval of 95%), the p-value for random effects, Egger’s p-value or visual inspection by funnel chart, I2, credibility value, and excess of significance (O/E and p-value) (1919. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-60..

Results

The search strategy initially found 296 articles. One duplicated article was excluded, leaving 295 articles assessed from their titles and abstract. The kappa agreement index between the two researchers for article inclusion or exclusion was 0.86. At the end of this stage, 144 articles were read in full to verify if they met the PECOS criteria. After the entire reading, 71 articles were excluded. In the following stage, the 73 articles included were verified for quality, out of which 36 were classified as having critical quality and therefore excluded. Finally, 37 articles were selected. (Figure 1).

Figure 1
Flowchart of study selection

The interobserver agreement on the quality of the selected articles was satisfactory. The item-to-item agreement for AMSTAR questions obtained by simple kappa was 0.83. The classification attributed to each article, in turn, was compared using weighted kappa, which got an excellent classification (kw=0.92). Moreover, the score obtained for each article, calculated from the simple sum of AMSTAR-2 items, was compared by the Bland-Altman method, showing the absence of classification bias (Figure 2).

Figure 2
Bland-Altman graph, used to assess the agreement of the quality classification score of articles included in the umbrella review (n=37)

Regarding the evidence found, of 37 included articles, 19 were published in 2012. For the epidemiological measures, six articles used mortality measures, eight used incidence measures only, and 23 used both measures. As for design study, ten studies conducted meta-analysis based on cohort studies, three used case-control studies, and 24 used both designs, estimating summary measures that considered the study design itself for the calculation.

Regarding study quality, studies were classified by AMSTAR-2 as low quality (n=15), medium quality (n=17), or high quality (n=5).

The main measure of random effects used was a relative risk (n=23). Eight studies used the odds ratio, whereas the six others used standardized measures such as the Proportional Mortality Ratio and Proportional Incidence Ratio. Furthermore, 26 articles showed no p-value for random effect measurements. However, to maintain the quality of the summary measure, 20 articles presented sensitivity analysis to obtain the measurement. No study had information about excess significance.

To verify the magnitude of heterogeneity in the studies, 24 articles presented the I22. Instituto Nacional de Câncer (BR). Estimativa 2020: incidência de câncer no Brasil. Rio de Janeiro: INCA; 2019. value, out of which six had I22. Instituto Nacional de Câncer (BR). Estimativa 2020: incidência de câncer no Brasil. Rio de Janeiro: INCA; 2019. values between 50% and 75%, indicating intermediate heterogeneity, and three had values above 75%, that is, high heterogeneity. Regarding publication bias analysis, 14 studies did not conduct the research using the Egger test. However, of the nine studies which conducted visual inspection using the funnel chart, only three presented symmetry, suggesting publication bias2020. Santos E, Cunha M. Interpretação crítica dos resultados estatísticos de uma meta-análise: estratégias metodológicas. Millenium [Internet]. 2013 [citado em 17 jun 2021];44:85-98. Disponível em: http://hdl.handle.net/10400.19/2273.
http://hdl.handle.net/10400.19/2273...
. Among those who took the Egger test (n=23), only two found evidence of bias (p<0.05).

The main exposures identified are exposure to inorganic dust (n=5), civil construction (n=3), exposure to solvents (n=4), services that use paint (n=4), agriculture (n=3), and civil construction (n=3). The most frequent cancers on the list were lung cancer and mesothelioma (n=15), bladder cancer (n=8), kidney cancer (21), and stomach, breast, and colon cancer (n=3 each) (8.10%).

The study assessed the heterogeneity of studies, quality of evidence obtained by AMSTAR, the strength of association, and the type of measure of association (that is if obtained from longitudinal data). The most robust and consistent results indicated associations between solvent exposure and multiple myeloma, asbestos and lung cancer, hydrocarbons and upper aerodigestive tract cancer, and occupational stress and colorectal cancer. Charts 1 and 2 and Table 1 summarize the study characteristics, describing the selected studies, the typology of the studies, and the assessment of quality and heterogeneity, respectively.

Chart 1
Overview of selected studies (n=37)

Chart 2
Description of the selected studies by typology and measure of association (n=37)

Table 1
Description of the selected studies by assessment of heterogeneity and quality of evidence (n=37)

Discussion

Cancer is a complex and multicausal disease. The component cause of several preventable cancers is occupational exposure. Unlike other risk factors, occupational risks are not caused by individual choice but by activities and institutions that do not protect workers from the harmful effects in work environments and production processes5858. Guimarães RM, Rohlfs DB, Baêta KF, Santos RD. Estabelecimento de agentes e atividades ocupacionais carcinogênicas prioritárias para a vigilância em saúde no Brasil. Rev Bras Med Trab.2019;17(2):254-9..

Corroborating the evidence from previous studies, this study indicates that lung, bladder, stomach, and colon cancers are consistently associated with occupational exposure to carcinogens. Service activities or activities composed of occupational groups with low schoolings, such as construction workers and drivers, are especially harmful.

Certain exposures well established in the literature99. Instituto Nacional de Câncer (BR). Coordenação Geral de Ações Estratégicas. Coordenação de Prevenção e Vigilância. Área de Vigilância do Câncer relacionado ao Trabalho e ao Ambiente. Diretrizes para a vigilância do câncer relacionado ao trabalho; organizadora Fátima Sueli Neto Ribeiro. Rio de Janeiro: INCA; 2012. were not described among the selected articles, including inorganic dust and pleura mesothelioma, vinyl polychloride and liver angiosarcoma, and solvents and leukemia. These exposures have been addressed from new theoretical models, as described in this study.

Mesothelioma, a rare tumor, is highly correlated with asbestos exposure5959. Gilham C, Rake C, Hodgson J, Darnton A, Burdett G, Wild JP, et al. Past and current asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS). Int J Epidemiol. 2018;47(6):1745-56.. Since this association has robust evidence, asbestos production and use have been banned for decades in European countries and the United States6060. Lemen RA. Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States. J Toxicol Environ Health B Crit Rev. 2016;19(5-6):250-65.. Studies on this type of exposure are expected to be conducted in other countries, where these substances have yet to be banned6161. Plato N, Martinsen JI, Sparén P, Hillerdal G, Weiderpass E. Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban. Epidemiol Health. 2016;38:e2016039..

Recent studies have sought to estimate the association of liver angiosarcoma with some occupational carcinogen exposure by minimizing the occurrence of bias from the possible interaction effect with alcohol and viral infections. Moreover, to further research this interaction, other studies have recently investigated the association between exposure and other forms of liver cancer, such as hepatocellular carcinoma6262. Fedeli U, Girardi P, Gardiman G, Zara D, Scoizzato L, Ballarin MN, et al. Mortality from liver angiosarcoma, hepatocellular carcinoma, and cirrhosis among vinyl chloride workers. Am J Ind Med. 2019;62(1):14-20.. Their latest method has been the in vitro study of the genotoxicity assessment of vinyl chloride6363. Guido M, Sarcognato S, Pelletti G, Fassan M, Murer B, Snenghi R. Sequential development of hepatocellular carcinoma and liver angiosarcoma in a vinyl chloride-exposed worker. Hum Pathol. 2016;57:193-6.), (6464. Fedeli U, Girardi P, Mastrangelo G. Occupational exposure to vinyl chloride and liver diseases. World J Gastroenterol. 2019;25(33):4885-91..

Furthermore, several studies suggest that leukemia risk may be associated with occupational or industrial exposures. However, the risk may vary according to the histological type of the disease6565. Blair A, Zheng T, Linos A, Stewart PA, Zhang YW, Cantor KP. Occupation and leukemia: a population-based case-control study in Iowa and Minnesota. Am J Ind Med. 2001;40(1):3-14.. Latest risk assessments have sought to establish genetic damage involving parental and intrauterine occupational exposures6666. Luijten M, Ball NS, Dearfield KL, B. Gollapudi B, Johnson GE, Madia F, et al. Utility of a next generation framework for assessment of genomic damage: A case study using the industrial chemical benzene. Environ Mol Mutagen. 2020;61(1):94-113.), while explanatory models seek to create bolder methods to isolate occupational exposure from environment exposure6767. Jephcote C, Brown D, Verbeek T, Mah A. A systematic review and meta-analysis of haematological malignancies in residents living near petrochemical facilities. Environ Health. 2020;19(1):53..

Studying impact measures is therefore crucial for an adequate interpretation. In this sense, the population attributable fraction (PAF) instrument estimates the fraction of cancer caused by occupational exposures6868. Bray F, Soerjomataram I. Population attributable fractions continue to unmask the power of prevention. Br J Cancer. 2018;118(8):1031-2..

PAFs are increasingly used to define cancer prevention priorities. However, though most authors recognize that occupational exposure focuses on lower socioeconomic status groups and more vulnerable workers, the instrument is mainly unknown regarding this type of exposure6969. Counil E, Henry E. Is it time to rethink the way we assess the burden of work-related cancer? Curr Epidemiol Rep. 2019;6:138-47.. Since this knowledge gap is related to the lack of data on the occupational pattern of exposures and the occurrence of cancer, establishing the circumstances and cancers related to occupation is essential to solve the problem.

Determining the attributable fraction thus highly depends on good data sources with full information. This aspect is one of the biggest obstacles in the study of occupational cancer, considering the lack of reliable information regarding occupational exposure to carcinogens. Besides the attributable fraction, the estimates of exposure proportion must also be determined by literature search and national data sources, using methodologies such as CARcinogen EXposure (CAREX) (7070. van Tongeren M, Jimenez AS, Hutchings SJ, MacCalman L, Rushton L, Cherrie JW. Occupational cancer in Britain. Exposure assessment methodology. Br J Cancer. 2012;107(Suppl 1):S18-26..

Though epidemiologists already face several obstacles to conducting studies on work-related cancer, those from middle- and low-income countries such as Brazil are even more challenged because of the lack of public policies and data sources and the likely greater occupational exposure7171. Iavicoli S, Driscoll TR, Hogan M, Iavicoli I, Rantanen JH, Straif K, et al. New avenues for prevention of occupational cancer: a global policy perspective. Occup Environ Med. 2019;76(6):360-2.. However, antagonistically, these locations are the ones that most need these studies.

While Brazil has extensive literature on carcinogenic factors such as diet and smoking, the country’s studies on work-related cancer are still embryonic. Moreover, national literature is restricted to a few occupational exposures that do not reflect current exposure but are used to estimate the prevalence of exposure to carcinogenic factors caused by work. This restriction limits the estimation of the fraction of work-related cancer. Some estimation attempts7272. Azevedo e Silva G, Moura L, Curado MP, Gomes FS, Otero U, Rezende LFM, et al. The fraction of cancer attributable to ways of life, infections, occupation, and environmental agents in Brazil in 2020. PLoS One. 2016;11(2):e0148761. are criticized - especially because of the highly specific criteria for agent selection since only those classified as group 1 by IARC1515. International Agency for Research Cancer [homepage na internet]. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans [citado em 13 mai 2021]. Disponível em: https://monographs.iarc.who.int/.
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) were considered. The classification of exposure intensity, which considers only occupational categories and economic activities definitively exposed7373. Otero UB, Mello MSC. Fração atribuível a fatores de risco ocupacionais para câncer no Brasil: evidências e limitações. Rev Bras Cancerol. 2016;62(1):43-5..

Furthermore, discussing cancer is part of one of the strategies of the Strategic Action Plan for Tackling Chronic Non-communicable Diseases in Brazil, which foresees research on the incidence, prevalence, morbidity and Mortality, and risk and protective factors for this disease7474. Malta DC, Silva AG, Teixeira RA, Machado IE, Coelho MRS, Hartz ZMA. Avaliação do alcance das metas do plano de enfrentamento das doenças crónicas não transmissíveis no Brasil, 2011-2022. Anais do IHMT. 2019;Suppl1:S9-16.. Another measure to discuss occupational cancer would be the articulated action with the General Coordination of Occupational Health of the Ministry of Health (CGST/MS), whose priority agenda includes occupational cancer surveillance1010. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância em Saúde Ambiental e do Trabalhador. DRT - Câncer Relacionado ao Trabalho, instruções para preenchimento. Brasília, DF; 2005.. Defining clear measures in the agenda is essential to prevent and identify solutions for the main health risks related to work7575. Takala J. Eliminating occupational cancer. Ind Health. 2015;53(4):307-9.. The history of the asbestos ban shows that slow and unaggressive measures cannot effectively reduce risk7676. Takala J, Hämäläinen P, Saarela KL, Loke YY, Manickam K, Tan WJ, et al. Global Estimates of the Burden of Injury and Illness at Work in 2012. J Occup Environ Hyg. 2014;11(5):326-37.), (7777. Siemiatycki J, Rushton L. Occupation: the need for continuing vigilance. In: Wild CP, Weiderpass E, Stewart BW, editors. World cancer report: cancer research for cancer prevention. Lyon: IARC. 2020, p. 127-36., requiring more ambitious goals for the future. Models that address occupational and personal risk factors and their interactions could thus improve the understanding of health risks and guide research and interventions.

Finally, understanding the mechanisms of biological plausibility for the main findings is essential. A mechanism by which solvents can induce cancer by damaging or altering DNA by mutation can also affect the immune system. Suppressed immunity will thus increase susceptibility to the virus, causing critical cytogenetic transformations and leading to multiple myeloma7878. Gold LS, Stewart PA, Milliken K, Purdue M, Severson R, Seixas N, et al. The relationship between multiple myeloma and occupational exposure to six chlorinated solvents. Occup Environ Med. 2011;68(6):391-9.. In turn, aerodigestive tract cancers develop by the progression of dysplastic lesions within the squamous epithelium and by mutation of the p53 gene, mechanisms induced by hydrocarbons7979. Roshandel G, Semnani S, Malekzadeh R, Dawsey SM. Polycyclic aromatic hydrocarbons and esophageal squamous cell carcinoma. Arch Iran Med. 2012;15(11):713-22.. Moreover, psychological stress can directly affect the risk of colorectal cancer by suppressing immune function or indirectly by changing physical activity and diet levels, which are recognized mechanisms for this type of neoplasm8080. Nielsen NR, Kristensen TS, Strandberg-Larsen K, Zhang ZF, Schnohr P, Grønbaek M. Perceived stress and risk of colorectal cancer in men and women: a prospective cohort study. J Intern Med. 2008;263(2):192-202..

These observations are relevant since they show the complexity of carcinogenesis mechanisms for these locations, to which occupational exposure is not a sufficient cause but a component cause. Understanding the cellular and molecular events caused by exposures to chemical carcinogens is therefore essential, reinforcing the role of epigenetics. At the same time, analysis of the factors leading to occupational exposure must consider the interaction effect of other behavioral factors.

This review has limitations. Studies classified as having critical quality were excluded from the selection. Study classification was conducted by weighting the classification criteria. However, since some of these criteria are suited for clinical trials, the absence of specific characteristics of AMSTAR-2 compromises classification regardless of real study quality. For example, the criterion “bias risk” makes any clinical trial critical since randomization presupposes a lack of bias. Observational studies - such as the selected articles - presuppose bias and analysis by statistical techniques. Another example is the absence of information on sources of finance, possibly indicating conflict of interest - a characteristic of drug intervention studies that does not apply to the selected studies.

Whenever possible, controlled vocabulary must be used. They are the subject descriptors on which articles are indexed in the database. Unfortunately, since the inclusion of descriptors is “operator-dependent,” a study on associations well established in the literature - such as the one between leukemia and benzene - does not have the descriptors “occupational cancer” or “work-related cancer,” it may be considered as biased. Moreover, the search would be biased if cancers of specific locations were included. Therefore, some studies of associations well established in the literature could have been lost in the search refinement. Furthermore, this review addressed all cancer that presented evidence of association with occupational exposure without selecting any location a priori.

Conclusion

Evidence shows associations between occupational exposures and types of cancer not initially foreseen in the guidelines for work-related cancer surveillance in Brazil. Though several systematic reviews and meta-analysis support the association between work and cancer, they are significantly heterogeneous. The causative associations reported could be imprecise since this study’s biases, such as residual confusion and selective reports of positive results, have been undersized or not even evaluated.

Therefore, Brazil requires further research and more consistent meta-analysis on relevant exposures and types of cancer, including exposure to inorganic dust and lung cancer and mesothelioma and exposure to solvents and hematological tumors. Evidence of cancer in other anatomical regions was less robust, showing signs of uncertainty or bias.

Investment in occupational epidemiology is thus essential to identify new associations of exposure and disease, surveil workers’ health, and emphasize the use of epidemiological findings of occupation in policy regulation and elaboration. For this, further specific meta-analysis should better reflect the demand for evidence in Brazil, including the association between exposure to asbestos and mesothelioma, exposure to particular solvents and hematological tumors (such as lymphocytic leukemia, non-Hodgkin lymphomas, and multiple myeloma). Finally, the Guidelines for Work-Related Cancer Surveillance99. Instituto Nacional de Câncer (BR). Coordenação Geral de Ações Estratégicas. Coordenação de Prevenção e Vigilância. Área de Vigilância do Câncer relacionado ao Trabalho e ao Ambiente. Diretrizes para a vigilância do câncer relacionado ao trabalho; organizadora Fátima Sueli Neto Ribeiro. Rio de Janeiro: INCA; 2012. should be revisited to cover increased surveillance actions.

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  • 4
    The authors report that this study was not presented at any scientific events.

Publication Dates

  • Publication in this collection
    25 July 2022
  • Date of issue
    2022

History

  • Received
    05 Nov 2020
  • Reviewed
    20 Feb 2021
  • Accepted
    02 Mar 2021
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