1. Cancer and work


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The first presentation for a workshop in Singapore and AIOH2013

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  • Need something on C x T from toxicology
  • Use Donaldson/Seaton paper on particle tox
  • 1. Cancer and work

    1. 1. Cancer and work John Cherrie INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK www.iom-world.org
    2. 2. Summary… • • • • Europe’s dirtiest factory What is cancer? Workplace cancers How do we identify carcinogens? • • • Toxicology Epidemiology Causality • The International Agency for Research on Cancer (IARC)
    3. 3. Europe’s dirtiest factory… • • • Malcolm Carhart died from lung cancer Fred Richards had bladder cancer and survived 300 other men who worked at the Phurnacite plant in South Wales had their health damaged by their work Mr Fred Richards
    4. 4. This was a coal carbonization plant
    5. 5. Mortality in the plant… • We carried out a mortality study in the plant in 1987 • • • Increased cancer mortality • • • • • 17 year follow-up 620 men included Lung – about 1.5x the expected numbers Stomach – 1.6x Prostate – 1.5x Bladder – 2.7x Non-melanoma skin cancer commonly reported
    6. 6. What is cancer? • Diseases where abnormal cells divide without control and are able to invade other tissues • • • • Cancer cells can spread through the blood and lymph systems The difference between a benign and a malignant tumour is the process of metastasis There are more than 100 different types of cancer Cancers are named according to the tissue where they originate, e.g. bladder cancer
    7. 7. Mutations… • Normal cells grow by division • • In a very small number of instances a cell may be damaged • • Mechanism controlled by our genes And cannot be repaired These cells should “selfdestruct” • A process known as apoptosis
    8. 8. Mutations… • • Cells may accumulate genetic transformations Typically several mutations are needed to cause cells to proliferate • • Grow uncontrollably This results in a mass of identical cells forming • • This is a tumour … but it may be benign!
    9. 9. Metastasis… • • • Two additional things characterise malignant tumours: Local invasion Metastasis
    10. 10. Main types of cancer… • • • • • Carcinoma - begins in the skin or tissues around internal organs Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood Lymphoma and myeloma - cancers that begin in the cells of the immune system Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord
    11. 11. Workplace cancers… • For most individual cancers it is not possible to be certain of the cause • • • • • Multi-causal Long latency, typically 40 years for carcinomas 20 years for leukaemia Most cancers are caused by the lifestyle we choose Some cancers are known to be associated with work or workplace exposures • e.g. lung cancer and diesel exhaust particulate
    12. 12. Key workplace carcinogens… • • There are more than Bladder, Bone, 20 types of cancer Brain, Breast, Cervix, Kidney, Larynx, that have been Leukaemia, Liver, Lung, linked to work… Lympho-haematopoietic, Main occupational Melanoma (eye), Mesothelioma, cancers in Britain Multiple myeloma, are Nasopharynx, NHL, NMSC, lung, mesothelioma, Oesophagus, non-melanoma skin Ovary, Pancreas, cancer (NMSC) and Sinonasal, Soft Tissue Sarcoma, Stomach, breast cancer Thyroid
    13. 13. Identifying carcinogens? • Epidemiology • • • • Studies of working populations Likely to be many other exposures present in the workplace(s) and differences in the lifestyle of individuals Studies need to have exposure over many decades Toxicology • • Experimental studies involving animals or cells, where the dose is controlled May be relatively short-term or may last two or three years
    14. 14. Risk and associations… • • • • • • Risk is the likelihood of an individual developing a disease Epidemiology measures risk A risk factor is a characteristic associated with a disease Exposure to a specific agent may be a risk factor Gender, age, dietary habits etc may also be risk factors Epidemiology identifies associations between risk factors and disease
    15. 15. Incidence prevalence and death… • Incidence is the rate of new cases of a disease • • • • generally reported as the number of new cases in a period, e.g. per year more meaningful when reported as a fraction of the population at risk, e.g., per 100,000 or per million Prevalence is the number of cases alive with the disease during a period of time (period prevalence) Incidence Death (= mortality)… Prevalence Death
    16. 16. Relative Risk and Standardised Mortality Ratio… • Results from a epidemiological study in a factory are generally expressed as a Standardised Mortality Ratio (SMR) • • • Ratio of observed to expected mortality Standardised for age and gender Relative Risk (RR) is the ratio of the disease rate in exposed persons compared to unexposed persons
    17. 17. Attributable fraction … • Attributable Fraction is the proportion of a disease in a specific population that would be eliminated if people were unexposed • So AF smoking is around 90% AF asbestos is around 80% • Age-standardized lung cancer death rates Death rate (per 100,000) NonSmoker smoker No asbestos 11 123 Asbestos 58 602 Hammond EC, Selikoff IJ, Seidman H. Asbestos exposure, cigarette smoking and death rates. Ann N Y AcadSci 1979;330:473-90.
    18. 18. Asbestos and cancer • • Earliest suspicions about cancer in the 1930s The link between asbestos and lung cancer was made in 1955 by Richard Doll • • Later confirmed in several epidemiological studies In 1960 Chris Wagner noted high incidence of mesothelioma in the crocidolite mines in South Africa • Also confirmed in epidemiological studies http://www.sciencemuseum.org.uk/broughttolife/peo ple/richarddoll.aspx
    19. 19. Heterogeneity of lung cancer findings…
    20. 20. Asbestos toxicology studies… • • • Gardiner (1942) found that “on grinding … they do not become more irritating but practically loose their power to provoke tissue reaction” Vorwald et al (1951) found that “The duration of exposure needed to develop an pulmonary reaction … is inversely proportional to the concentration of long fibres…” 1960s Merle Stanton at the National Cancer Institute studied mesothelioma induction by fibres using an implantation technique onto the pleura
    21. 21. Further toxicity studies have shown… • Fibres are harmful because… • • • • they are thin (d< 3 m) they are long (l> 5 m) and because of their shape (l/d> 3) and they persist in the lung 21
    22. 22. However… • • Animals are not humans! Inhalation toxicity studies are often carried out with small groups of animals at very high air concentrations • • Toxicity studies now often carried out with cellular systems • • Danger of unrepresentative findings from overloading the lungs in vitro versus in vivo Toxicity data not a good indicator of risk
    23. 23. Guidelines for Judging Causality • • Strength of Association Consistency • • Specificity • • • An exposure gives a single outcome Temporality Biological gradient • • • • • Are results “similar” across studies Response related to magnitude of exposure Plausibility Coherence Experiment Analogy http://www.sciencemuseum.org.uk/broughttolife/people/austinh ill.aspx
    24. 24. IARC monograph programme… • The International Agency for Research on Cancer (IARC) Monographs published since 1971 • • • • • • • Chemicals Complex mixtures Occupational exposures Physical and biological agents Lifestyle factors More than 900 agents have been evaluated A source of scientific information on potential carcinogens and support for prevention
    25. 25. The IARC Monographs… • The International Agency for Research on Cancer (IARC) classify carcinogens as: • • • • • Group 1: The agent is carcinogenic to humans Group 2A: The agent is probably carcinogenic to humans Group 2B: The agent is possibly carcinogenic to humans Group 3: The agent is not classifiable as to its carcinogenicity to humans Group 4: The agent is probably not carcinogenic to humans http://monographs.iarc.fr
    26. 26. Summary… • • • • • Cancer is a multitude of different diseases, each with a variety of potential causes Many exposures in the workplace can cause cancer Epidemiology and Toxicology allow us to identify causal associations between exposures and specific cancers Risks are best quantified by epidemiology IARC provides a reliable assessment of human carcinogenicity