Occupational Cancer: Causes, Prevention and Global Burden
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Occupational Cancer: Causes, Prevention and Global Burden
- 1. OCCUPATIONAL CANCER Professor E.E.U. Akang OCCUPATIONAL HEALTH UNIT, DEPT. OF PREVENTIVE MEDICINE & PRIMARY CARE, COLLEGE OF MEDICINE, UNIVERSITY OF IBADAN 2011/2012 ACADEMIC CALENDAR MPH (OH) 0HS 702 24 October 2012
- 2. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 3. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 4. What is cancer? • A malignant (“potentially lethal”) neoplasm (“new growth”) that invades normal tissues and spreads (metastasises) to distant sites • Neoplasms are growths resulting from clonal proliferation of cells following progressive accumulation of hereditary and acquired insults resulting in mutations of genes that control cell proliferation and cell death
- 5. What is occupational cancer? • Cancer specifically attributed to significant levels of exposure to an agent* in the workplace and occurring among substantial numbers of workers. • Substantial: > 10,000 workers • Significant: As much as, or more than, in the general environment *An agent that has been causally linked with development of cancer is called a carcinogen Siemiatycki et al, Environ Hlth Persp, 2004, http://www.ehponline.org
- 6. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 7. What is the global and national burden of cancer? • 5 million female and 6 million male new cancer cases worldwide (of which 100,000 occur in Nigeria) annually • >6 million deaths worldwide annually • >50% of patients with cancer live in developing countries, which have <10% of the resources for cancer therapy
- 8. Global statistics on cancer, 2002
- 9. What is the global burden of occupational cancer? • POPULATION ATTRIBUTABLE FRACTION (RISK PER CENT) This is defined as the fraction (percentage) of the diseased persons in the population whose disease would have been prevented had the exposure been absent In the case of occupational cancers, a crude estimate for this percentage is between 2-10%
- 10. What is the relevance of occupational cancer epidemiology? 1. 50% of known human carcinogens are substances found principally in the workplace 2. Many cases of cancer are directly attributable to occupational exposure 3. Control measures can often be implemented once an occupational carcinogen has been identified 4. The discovery of occupational carcinogens has importance outside the factory walls 5. Provides a basis for compensating victims 6. Improves our understanding of carcinogenesis Siemiatycki et al, Environ Hlth Persp, 2004, http://www.ehponline.org 10
- 11. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 12. What do we know about carcinogenesis in general? Carcinogenesis is a multi-hit, multi-stage process Results from the cumulative effect of repeated prolonged exposure to environmental carcinogens in concert with inherent genetic/other susceptibility •>80% NATURE- environment- <10% NURTUREgenes Radiation, Chemicals, Viruses 60% of all cancers are PREVENTABLE Carcinogens may be 1. Genotoxic (interact with and alter DNA) 2. Epigenetic (affect gene expression)
- 13. Historical landmarks • 1775, Percivall Pott in London- scrotal cancer among chimney sweeps • 1895, Rehn, in Germany- cluster of three cases of bladder cancer in workers at a local factory producing aniline dyestuffs from coal tar • Early 20th century- certain constituents of tar, soot, and oils, known as polycyclic aromatic hydrocarbons, were found to cause cancer in laboratory animals • 1970, IARC recommended that a compendium on carcinogenic chemicals be prepared by experts
- 14. What do we know about occupational carcinogens?- 1 Exposure may be acquired via 1 INHALATION average concentration of the substance in the breathing zone over a reference period (8 hours for long-term, and 15 minutes for short-term exposure) 2 DERMAL CONTACT potential dose rate predominantly to the hands and forearms (2000 cm2) is calculated using a mathematical model 3 INGESTION not quantifiable
- 15. What do we know about occupational carcinogens?- 2 Occupationally related cancers are characterized by a long latent period—time between first exposure and clinical presentation (usually >1015 years) and up to 40-50 years in some cases (i.e. presentation can be in retirement rather than while still at work). An occupationally related tumour does not differ substantially, either pathologically or clinically, from its “naturally occurring” counterpart.
- 16. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 17. IARC classes of carcinogens On the basis of epidemiological, animal and in vitro experimental studies, occupational agents linked with cancer have been categorised into 4 major groups by the IARC 1 2A 2B 3 4 Carcinogenic to humans (21%) Probably carcinogenic to humans (16%) Possibly carcinogenic to humans (63%) Not classifiable Not carcinogenic to humans
- 18. GROUP 1 (DEFINITE)CARCINOGENS 40% (40) IARC group 1 carcinogens are occupational. Others include radiation, viruses and lifestyle factors PHYSICAL AGENTS ASSOCIATED CANCERS Ionizing radiation Breast cancer, leukaemia, skin cancer Unltraviolet light Skin cancer Asbestos Lung cancer, mesothelioma CHEMICAL AGENTS ASSOCIATED CANCERS Arsenic Skin cancer, lung cancer Vinyl chloride Liver angiosarcoma Aromatic amines Bladder cancer
- 19. IARC Group 1 occupations and industries Aluminium production Haematite mining Auramine Iron and steel founding Boot and shoe Isopropanol Coal gasification Magenta Coke production Painter Furniture & cabinet making Rubber industry 19
- 20. GROUP 2A (PROBABLE) CARCINOGENS 30 IARC group 2A carcinogens are occupational. CHEMICAL AGENTS ASSOCIATED CANCERS Polyaromatic hydrocarbons Lung, bladder & skin cancer Wood & Fossil fuel products Skin cancer Plastic & rubber byproducts Bladder cancer Chlorinated hydrocarbons Several cancers Inorganic lead compounds Lung cancer Aromatic amine dyes (e.g. benzidine-based dyes) Bladder cancer
- 21. IARC Group 2A occupations and industries Art glass manufacturing • Cobalt metal manufacturing Hairdresser or barber Petroleum refining 21
- 22. IARC Group 2B occupational carcinogens 117 IARC group 2B carcinogens are occupational. • • • • • • Refractory ceramic fibres Nickel alloys Carbon black Gasoline engine exhaust Gasoline Bitumens • • • • • • Styrene Acrylonitrile Chloroform Dichloromethane Some pesticides Welding fumes 22
- 23. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 24. Strategies for discovering occupational carcinogens • Epidemiological surveys • Animal experimentation (toxicological studies) • Other experimental studies Ames mutagenicity test (Salmonella, E. coli) Mammalian in vitro mutagenicity test (Chinese hamster lung derived cells) Mouse in vivo clastogenicity assay
- 25. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 26. Primary prevention of occupational cancer • Recognition of hazards and risks • Education of management and workforce • Elimination of exposure (substitution, automation) • Reduction of exposure • Provision of personal protective equipment • Limiting access • Adequate facilities for showering, changing, etc. • Legislative provisions Veys, 1996, http://dx.doi.org/10.1136/bmj.313.7057.615
- 27. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 28. Topical issues in occupational cancer •May be a significant and under estimated problem in developed and developing countries •Challenges include exposure assessment, sample size, confounding factors, manpower to conduct research, ethical issues, legislation (particularly in developing countries) •Confounding factors include age, social class, “healthy worker” effect •Interaction- different joint effect of 2+ carcinogens (i.e. synergy (multiplicative) and antagonism)
- 29. Lecture Outline • • • • • • • • Definitions (Cancer, Occupational cancer) Epidemiological considerations Carcinogenesis- basic principles Classes (IARC groups) of carcinogens Strategies for identification of carcinogens Primary prevention of occupational cancer Topical issues Closing remarks
- 30. Closing remarks • Occupational cancer affords significant opportunities for research • Cancers related to the workplace can be reduced by the implementation of primary prevention and by increased vigilance of occupational health workers • Advocacy is essential to raise awareness of general public, legislators, employers and workers
- 31. THANKS FOR LISTENING! A little learning is a dang'rous thing; Drink deep, or taste not the Pierian spring. 31
Hinweis der Redaktion
- Industrial workers have long served as sentinels for the general population with regard to environmental hazards. Although many chemicals found in the industrial setting can also be found in the environment, industrial workers often have more intense and prolonged exposures to chemicals than does the general population. Consequently, cancers in humans caused by these substances are often first noted in the workplace. Many of the well-established and suspected chemical carcinogens were identified through occupational studies. One of the earliest examples occurred more than 200 years ago when, in 1775, Percivall Pott, a London surgeon, described a high frequency of cancer of the scrotum among chimney sweeps. A century later, other scientists noted similar cancers among gas plant workers in Germany and among oil shale workers in Scotland. Some 40 years later, certain constituents of tar, soot, and oils, known as polycyclic aromatic hydrocarbons, were found to cause cancer in laboratory animals, thus identifying the specific substances causing cancer among workers in these occupations. Preventive action was taken in Denmark, where the chimney sweeps' guild, spurred by Pott's report, urged its members to take daily baths. The success of this action was noted in a report in the 1892 British Medical Journal, "Why Foreign Sweeps Do Not Suffer From Scrotal Cancer”, which pointed out that the sweeps of Northern Europe seemed to benefit from this hygiene measure, but English sweeps, apparently ignoring such recommendations, continued to develop cancer. This saga became the model for many later investigations of workplace carcinogens. Such studies have focused on Observation of unusual cancers, or a high incidence of common cancers, among groups of workers Searches for responsible agents Demonstration that the agent can cause cancer in laboratory animals; and Implementation of preventive programs.
- Cancer is the colloquial expression used by medical workers and laypersons alike to refer to malignant neoplasm. A neoplasm is a lesion formed by autonomous clonal expansion of abnormal cells that have a selective growth advantage over their neighbouring cells; and a malignant neoplasm is one which, if not promptly eradicated, will inexorably invade surrounding tissues and vascular channels, metastasize to distant sites and will inevitably result in death of the afflicted patient.
- Occupational cancer may be defined as cancer that may be specifically attributed to significant (i.e. more so than in the general environment) levels of exposure to an agent in the workplace and occurring in substantial (i.e. greater than 10,000) numbers of workers.
- Cancer is a cosmopolitan problem, afflicting approximately five million women and six million men annually, worldwide (Ferlay et al, 2004). It is the second leading cause of death among both males and females in developed countries (Pamies and Crawford, 1996). Twenty per cent of all deaths in the US and UK are due to cancer, compared to 6-13% in developing countries. In the United States alone, 4.6 million new cases were reported to the National Cancer Data Base between 1985-1994 (Menck et al., 1998). Paradoxically, over 50% of cancer patients live in developing countries, which have less than 10% of the human resources, finance and technological infrastructure to effectively tackle the problems of cancer prevention, diagnosis and care (Durosinmi, 2006). In Nigeria alone, it has been estimated that there are 100,000 new cases of cancer per year, which was expected to increase to about 500,000 cases annually by the year 2010 (Durosinmi, 2006). The total burden of cancer may be expected to escalate proportionally with advances in the control of communicable diseases, increasing longevity, and ever-increasing industrialization of both third world and developed countries.
- This composite bar chart indicates the enormity of the problem of cancer in graphic detail. The five major cancer killers world-wide are lung cancer, female breast cancer, cancer of the large bowel, gastric cancer and male prostate cancer.
- Cancer is a cosmopolitan problem, afflicting approximately five million women and six million men annually, worldwide (Ferlay et al, 2004). It is the second leading cause of death among both males and females in developed countries (Pamies and Crawford, 1996). Twenty percept of all deaths in the US and UK are due to cancer, compared to 6-13% in developing countries. In the United States alone, 4.6 million new cases were reported to the National Cancer Data Base between 1985-1994 (Menck et al., 1998). Paradoxically, over 50% of cancer patients live in developing countries, which have less than 10% of the human resources, finance and technological infrastructure to effectively tackle the problems of cancer prevention, diagnosis and care (Durosinmi, 2006). In Nigeria alone, it has been estimated that there are 100,000 new cases of cancer per year, which was expected to increase to about 500,000 cases annually by the year 2010 (Durosinmi, 2006). The total burden of cancer may be expected to escalate proportionally with advances in the control of communicable diseases, increasing longevity, and ever-increasing industrialization of both third world and developed countries.
- Carcinogenesis- General principles Cancer formation is a multistage process resulting from the cumulative effects of multiple extrinsic physical, chemical and biological agents interacting with endogenous host factors. Generally, it is estimated that cancer is contributed to in 80% of cases by environmental factors, and in only a minority of cases (probably less than 10%) are primary genetic disorders responsible for cancer. Some of the environmental factors implicated in carcinogenesis include Physical agents (ultraviolet, X and gamma irradiation) Chemical agents (polycyclic aromatic hydrocarbons, aromatic amines/azo dyes, alkylating agents and natural carcinogens such as aflatoxins and nitrosamines), and Biological agents (Hepatitis B and C viruses, Human T cell lymphoma virus type 1, Human Papilloma Virus types 16 and 18, Epstein-Barr virus and Human Herpes Virus type 8/Kaposi Sarcoma Herpes Virus, Helicobacter pylori, Schistosoma haematobium and Clonorchis sinensis, for example). Endogenous host factors such as immune suppression, endocrine stimulation (prostate, breast, liver, thyroid and endometrial cancer), diet (vitamin A/C deficiency, high fat diet, low fibre diet), the occurrence of premalignant lesions (dysplasia, metaplasia, chronic inflammation and hamartomas) and hereditary or genetic factors may also contribute to carcinogenesis. Epidemiological studies contribute to a better knowledge of aetiological risk factors and occupations responsible for the outcome of these cancers and allow quantification of the risk of cancer linked to different situations of exposure. Beside classical epidemiological studies, molecular epidemiology aims at identifying molecular targets of occupational agents. This approach may allow a better knowledge of the part played by occupational agents in these multifactorial diseases (Pairon, 2002).
- 1775, Percivall Pott, a London surgeon, described a high frequency of cancer of the scrotum among chimney sweeps. A century later, other scientists noted similar cancers among gas plant workers in Germany and among oil shale workers in Scotland. in 1895, Rehn, a German surgeon working in Frankfurt, treated a cluster of three cases of bladder cancer in workers at a local factory producing aniline dyestuffs from coal tar. Some 40 years later, certain constituents of tar, soot, and oils, known as polycyclic aromatic hydrocarbons, were found to cause cancer in laboratory animals
- In the occupational setting, cancer may be acquired by inhalation, dermal contact or by ingestion (Env. Hlth. Criteria, WHO, 1999). Inhalation exposure is assessed by determining the average concentration of the substance in the breathing zone averaged over a reference period (8 hours for long-term, and 15 minutes for short-term exposure). Exposure to skin is determined by calculating the potential dose rate predominantly to the hands and forearms (2000 cm2) using a mathematical model. Cumulative inhalation or dermal exposure is determined by the product of the average intensity and time. Ingestion exposure usually cannot be quantified. It must be noted that the methods of assessment of carcinogen exposure have not been standardised to universally accepted levels
- Studies of occupational groups remain an important component of the current effort to identify the causes of human cancer. A listing and summary of evidence regarding occupational factors that may cause human cancer can be found in some critical monographs published by the International Agency for Research on Cancer (IARC) and the World Health Organisation, respectively. These volumes deal with cancer risks from individual chemicals, and mixtures of chemicals, in selected occupations or industries, and review issues such as risk assessment, testing for biomarkers, and testing for carcinogenicity. The evaluations in the IARC monographs are based on epidemiological data from studies in humans, bioassays in animals, and data from short-term tests and laboratory experiments. For the monographs, experts in carcinogenesis evaluate the available data for individual chemicals, chemical groups, industrial processes, or specific occupations and assign each to a category of risk. When there is enough evidence from epidemiologic studies to support a causal association with cancer, the chemical, chemical group, process, or exposure is assigned to Group 1 (e.g., asbestos, benzene, chromium, vinyl chloride, coke production, furniture manufacturing, and nickel refining). Chemicals that are carcinogenic in laboratory animals, but for which human data may be limited or lacking, are typically placed in Group 2. Those considered to be probably carcinogenic to humans appear in Group 2A (e.g., acrylonitrile, cadmium, formaldehyde, and silica), and those considered to be possibly carcinogenic to humans are placed in Group 2B (including butadiene, carbon tetrachloride, chlorophenoxy herbicides, DDT, styrene, and tetrachloroethylene). The other categories are considered not classifiable as to carcinogenicity (Group 3), or not carcinogenic to humans (Group 4). The agents carcinogenic to humans and those probably or possibly carcinogenic to humans do not fall into any particular class of substances. They include metals (arsenic, chromium, nickel, cadmium), solvents (benzene, styrene, carbon tetrachloride, dichloromethane), organic and inorganic dusts (leather or wood dusts, asbestos, silica), chemicals used to construct polymers (acrylonitrile, formaldehyde, vinyl chloride), and pesticides (ethylene oxide, amitrole, chlorophenoxy herbicides, DDT, toxaphene).
- Studies of occupational groups remain an important component of the current effort to identify the causes of human cancer. A listing and summary of evidence regarding occupational factors that may cause human cancer can be found in some critical monographs published by the International Agency for Research on Cancer (IARC) and the World Health Organisation, respectively. These volumes deal with cancer risks from individual chemicals, and mixtures of chemicals, in selected occupations or industries, and review issues such as risk assessment, testing for biomarkers, and testing for carcinogenicity. The evaluations in the IARC monographs are based on epidemiological data from studies in humans, bioassays in animals, and data from short-term tests and laboratory experiments. For the monographs, experts in carcinogenesis evaluate the available data for individual chemicals, chemical groups, industrial processes, or specific occupations and assign each to a category of risk. When there is enough evidence from epidemiologic studies to support a causal association with cancer, the chemical, chemical group, process, or exposure is assigned to Group 1 (e.g., asbestos, benzene, chromium, vinyl chloride, coke production, furniture manufacturing, and nickel refining). Chemicals that are carcinogenic in laboratory animals, but for which human data may be limited or lacking, are typically placed in Group 2. Those considered to be probably carcinogenic to humans appear in Group 2A (e.g., acrylonitrile, cadmium, formaldehyde, and silica), and those considered to be possibly carcinogenic to humans are placed in Group 2B (including butadiene, carbon tetrachloride, chlorophenoxy herbicides, DDT, styrene, and tetrachloroethylene). The other categories are considered not classifiable as to carcinogenicity (Group 3), or not carcinogenic to humans (Group 4). The agents carcinogenic to humans and those probably or possibly carcinogenic to humans do not fall into any particular class of substances. They include metals (arsenic, chromium, nickel, cadmium), solvents (benzene, styrene, carbon tetrachloride, dichloromethane), organic and inorganic dusts (leather or wood dusts, asbestos, silica), chemicals used to construct polymers (acrylonitrile, formaldehyde, vinyl chloride), and pesticides (ethylene oxide, amitrole, chlorophenoxy herbicides, DDT, toxaphene).