The first presentation for a workshop in Singapore and AIOH2013

1. Cancer and work
John Cherrie
INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK
www.iom-world.org

2. Summary…
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Europe’s dirtiest factory
What is cancer?
Workplace cancers
How do we identify carcinogens?
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Toxicology
Epidemiology
Causality
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The International Agency for Research on
Cancer (IARC)

3. Europe’s dirtiest factory…
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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. This was a coal carbonization
plant

5. Mortality in the plant…
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We carried out a mortality
study in the plant in 1987
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Increased cancer mortality
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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. What is cancer?
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Diseases where abnormal cells
divide without control and are
able to invade other tissues
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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. Mutations…
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Normal cells grow by
division
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In a very small number of
instances a cell may be
damaged
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Mechanism controlled
by our genes
And cannot be repaired
These cells should “selfdestruct”
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A process known as apoptosis

8. Mutations…
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Cells may accumulate
genetic transformations
Typically several
mutations are needed to
cause cells to proliferate
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Grow uncontrollably
This results in a mass of
identical cells forming
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This is a tumour
… but it may be benign!

9. Metastasis…
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Two
additional
things
characterise
malignant
tumours:
Local invasion
Metastasis

10. Main types of cancer…
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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. Workplace cancers…
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For most individual cancers it is not
possible to be certain of the cause
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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
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e.g. lung cancer and diesel exhaust particulate

12. Key workplace carcinogens…
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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. Identifying carcinogens?
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Epidemiology
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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
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Experimental studies involving animals or
cells, where the dose is controlled
May be relatively short-term or may last two or
three years

14. Risk and associations…
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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. Incidence prevalence and death…
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Incidence is the rate of new cases of a
disease
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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. Relative Risk and Standardised
Mortality Ratio…
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Results from a epidemiological study
in a factory are generally expressed
as a Standardised Mortality Ratio
(SMR)
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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. Attributable fraction …
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Attributable Fraction is the proportion of a
disease in a specific population that would
be eliminated if people were unexposed
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So AF smoking is
around 90%
AF asbestos is
around 80%
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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. Asbestos and cancer
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Earliest suspicions about
cancer in the 1930s
The link between asbestos
and lung cancer was made
in 1955 by Richard Doll
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Later confirmed in several
epidemiological studies
In 1960 Chris Wagner noted high
incidence of mesothelioma in the
crocidolite mines in South Africa
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Also confirmed in epidemiological
studies
http://www.sciencemuseum.org.uk/broughttolife/peo
ple/richarddoll.aspx

19. Heterogeneity of lung cancer
findings…

20. Asbestos toxicology studies…
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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. Further toxicity studies have
shown…
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Fibres are harmful because…
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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
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22. However…
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Animals are not humans!
Inhalation toxicity studies are often
carried out with small groups of animals
at very high air concentrations
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Toxicity studies now often carried out
with cellular systems
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Danger of unrepresentative findings from
overloading the lungs
in vitro versus in vivo
Toxicity data not a good indicator of risk

23. Guidelines for Judging Causality
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Strength of Association
Consistency
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Specificity
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An exposure gives a single outcome
Temporality
Biological gradient
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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. IARC monograph programme…
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The International Agency for Research on
Cancer (IARC) Monographs published since
1971
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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. The IARC Monographs…
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The International Agency for Research on
Cancer (IARC) classify carcinogens as:
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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. Summary…
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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