Presentation from Manolis Kogevinas, Head of the Cancer Programme at ISGlobal, on occupational cancer. Epidemiology in Occupational Health Conference - EPICOH 2017

1. Occupational Cancer in the 21st
century
Manolis Kogevinas MD, PhD
Barcelona Institute for Global Health (ISGlobal)
manolis.kogevinas@isglobal.org
@KogevinasM
EPICOH 2017, Edinburgh

2. Occupational Cancer: main messages
• Around 4% of all cancers – but varies; old exposures are
still here!
• Workplace exposures decrease in High Income and
increase in Middle Income Countries (LowIC?)
• New risks occur (or are newly identified)
• Research in occupational cancer historically very
productive; major recent findings and some failures
• Prevention of occupational cancer a global issue!

4. •18910 production workers and
sprayers from 10 countries
•4 deaths from soft-tissue sarcoma

5. Dioxins research: studies in workers became conclusive
only when we provided valid exposure assessment models
Serum levels of TCDD in 253 US workers,
according to years of exposure. (Fingerhut et al,
NEJM 1991)
Concentration of TCDD in serum of New Zealand
applicators in relation to total months spent
spraying 2,4,5-T. (Smith et al, JNCI. 1992)

6. Dioxins research: animal and mechanistic data
important to identify as human carcinogen
Very strong evidence in experimental animals in relation to
multiple neoplasms
Very strong supporting mechanistic data: There is strong evidence
to support a receptor mediated mechanism that operates in
humans for carcinogenesis associated with 2,3,7,8-
tetrachlorodibenzo-para-dioxin, … The conservation of the aryl
hydrocarbon receptor and the related signalling pathways and
responses across species, including humans, add additional
strength to the notion that this mechanism is active in humans.

7. (Doll & Peto 1981)

8. Incidence 3.795.000 * 4% = 151.800
Mortality 1.933.000 * 4% = 77.300
(incidence data from Globocan, IARC 2012)
4% of all cancers in Europe,
both sexes (WHO Euro region)

9. Incidence 3.795.000 * 4% = 151.800
Mortality 1.933.000 * 4% = 77.300
(incidence data from Globocan, IARC 2012)
4% of all cancers in Europe,
both sexes (WHO Euro region)
(but is 4% a valid estimate for today?)

10. Rubber-Tire Industry “Michelin”, England

11. The burden of cancer at work:
estimation as the first step to
prevention (L Rushton, OEM 2008)
• In 2004, 78237 men and 71666 women died
from cancer in the UK
• Of them, 7317 (4.9%) can be atributed to
exposures at work. Men 6259, 8%; Women:
1058, 1.5%
• 13 338 (4.0%) new cases of cancer

12. Prediction of mortality from mesothelioma in
England (J Peto et al., Lancet 1996)

13. Global Burden of Disease – Deaths and DALYs from
occupational carcinogens by Social Development
Index (SDI)
High-middle SDI
High SDI
Middle SDI
Low-middle SDI
Low SDI
(http://ghdx.healthdata.org/gbd-results-tool)

14. Occupational cancer
Present and future

15. Trends in occupational exposure to
carcinogens
Reduction of number of workers exposed through wider
changes in production (in Western Europe/N America) and
transfer to 3rd world countries

16. Textiles, Bangladesh
C. Salgado

17. Ship dismantling
Bangladesh
C. Salgado

19. World mine production of asbestos from 2007 to
2012 (in 1000 metric tons)

21. Trends in occupational exposure to
carcinogens
Reduction of number of workers exposed through wider
changes in production (in Western Europe/N America)
More efficient control of exposure to known carcinogens
in HIC through elimination, substitution, and specific and
general measures of hygiene and security

22. Exposure to styrene among workers (laminators)
in the reinforced plastics industry, 1960-1990

23. Trends in occupational exposure to
carcinogens
Reduction of number of workers exposed through wider
changes in production (in Western Europe/N America)
More efficient control of exposure to known carcinogens
in HIC through elimination, substitution, and specific and
general measures of hygiene and security
 Introduction of new materials and technologies that
could be associated with increased risks or changes in work
conditions and labour force that could have a direct or
indirect association with cancer occurrence

24. www.creal.cat
Carcinogenicity of shift work
IARC (WHO), 2007
“Shift work involving circadian disruption is
probably carcinogenic to humans” (Group 2A)
based on…
• Sufficient evidence from (>20) animal studies
showing the carcinogenicity of light during night
• Limited evidence from epidemiological studies showing
higher risks for breast cancer among female night workers
Straif K et al, 2007; IARC Monographs Vol 98, 2010

25. Melatonin (aMT6s). Mesor (circadian mean) and acrophase
(peak time) in day and night workers. Cosinor curves.
(Papantoniou, CEBP 2014)

26. World’s population 2017: 7 billion
(Modified from Hans Rosling)

27. World’s population 2100
(Modified from Hans Rosling)

28. Unemployment and vulnerable employment trends
and projections, 2007–18
(World Employment and Social Outlook: Trends 2017, ILO 2017)

29. Research in Occupational Cancer

30. Themes EPICOH2016 Barcelona

31. Criteria for evaluating research
Novelty: Will research in a specific area produce new
knowledge?
Importance to People: Will the life and well-being of
many populations be positively affected?
Impact on Policy: Will research in a specific area produce
knowledge that meaningfully informs evidence-based
health policies and prevention?
Technical Innovation and Development: Will research
produce new technologies and help economic
development?
(Kogevinas, Environ Epi 2017)

32. • The case-series phase
• SMR study phase (high risks, fairly simple designs)
Phases in occupational cancer research
(overlapping)

33. Creech JL Jr, Johnson MN. Angiosarcoma of liver in the
manufacture of polyvinyl chloride
(J Occup Med. 1974; 16: 150-1)
Between September 1967 and December 1973, 4 cases
of angiosarcoma of the liver were diagnosed among men
employed in the polyvinyl chloride polymerization section
of a B.F. Goodrich plant near Louisville, Kentucky.
Angiosarcoma of the liver is an exceedingly rare tumor. It
is estimated that only about 25 such cases occur each
year in the United States

34. Principal evidence leading to the identification of
occupational carcinogens (Group 1 IARC)
Case Case-Control Cohort Cohort Mechanistic
Carcinogen Reports Retrospective Prospective Data
Aminobiphenyl x
Aromatic amines x x
Arsenic x x
Asbestos x
Benzene x x x
Benzidine x x
Beryllium x
Cadmium x
Chloromethyl ethers x
Chromium x
Dioxin x x
Erionite x
Ethylene oxide x x
Mustard gas x
Nickel x
Pitch, Tar, Sorts x
Radon x
Silica x
Talc x x
Vinyl chloride x
Wood dust x x x

35. • The case-series phase
• SMR study phase (high risks, fairly simple designs)
• Advanced exposure assessment phase (development
of advanced methods for exposure assessment in cohort
and case-control studies)
Phases in occupational cancer research
(overlapping)

36. Siemiatycki J, Richardson L, Gérin M, Goldberg M, Dewar R, Désy M,
Campbell S, Wacholder S. Associations between several sites of cancer and
nine organic dusts: results from an hypothesis-generating case-control study
in Montreal, 1979-1983. Am J Epidemiol. 1986; 123: 235-49.

37. Siemiatycki J, Richardson L, Gérin M, Goldberg M, Dewar R, Désy M,
Campbell S, Wacholder S. Associations between several sites of cancer and
nine organic dusts: results from an hypothesis-generating case-control study
in Montreal, 1979-1983. Am J Epidemiol. 1986; 123: 235-49.
Lifetime Work
History (CAPI)
Job-Specific
Modules
Follow-up Questionnaire
2
3
Estimating Exposure
Levels for n agents
Developing Exposure
Indices
Finalize Assignments
After Systematic
Review
Merging
5
4
1
Mustafa Dosemeci and many others

38. Ana, carrying
the 63
occupational
modular
questionnaires.
EPICURO study
(Spanish bladder
Cancer Study)

39. • The case-series phase
• SMR study phase (high risks, fairly simple designs)
• Advanced exposure assessment phase (development
of advanced methods for exposure assessment in cohort
and case-control studies)
• Molecular epidemiology phase (incorporation of
molecular and omic techniques)
Phases in occupational cancer research
(overlapping)

40. Use of mechanistic data – the case
of ethylene oxide (IARC 1994)

41. • The case-series phase
• SMR study phase (high risks, fairly simple designs)
• Advanced exposure assessment phase (development
of advanced methods for exposure assessment in cohort
and case-control studies)
• Molecular epidemiology phase (incorporation of
molecular and omic techniques)
• Newer trends: exposome (external and internal and
pathways); pooled analyses (sharing of data); record
linkage (big data); emphasis on cohort studies (with
exceptions); new approaches to causal inference
Phases in occupational cancer research

43. Evaluations of the International Agency for
Research on Cancer (IARC) (www.iarc.fr)
• Group 1. The agent (mixture, exposure
circumstance) 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

44. Occupational Human carcinogens
(Group 1- IARC)
• 118 agents in Group 1
• 57 are occupational or also occur in the occupational
environment (e.g. aflatoxins, SHS, radiations etc)
• Of those, 36 were identified as Group 1 before the year
2000, and 21 after the year 2000
(numbers of occupational carcinogens may differ from other
summaries)

45. Probable Occupational Human
carcinogens (Group 2A- IARC)
• 81 agents in Group 2A (probable carcinogens)
• 48 are occupational
• Of those, 20 were identified as Group 2A before the
year 2000, and 28 after the year 2000
• Use of evidence on mechanisms very important for
this group (upgrade from 2B-possible to 2A-probable)
(numbers of occupational carcinogens may differ from
other summaries)

46. Major Occupational Human carcinogens (Group
1/2A- IARC) and period of identification
Agent-England After 2000 Agent-Catalonia After 2000
Asbestos UV-solar
Silica Shift work x
Diesel engine exhaust x Diesel engine exhaust x
Radon x? Radon x?
Work as a painter Silica
Mineral oils (metal
workers, printing
industry)
PAHs
Second Hand Smoke x Benzene
Work as a welder x Chromium VI
Dioxins

47. Major Occupational Human carcinogens (Group
1/2A- IARC) and period of identification
Agent-England After 2000 Agent-Catalonia After 2000
Asbestos UV-solar
Silica Shift work x
Diesel engine exhaust x Diesel engine exhaust x
Radon x? Radon x?
Work as a painter Silica
Mineral oils (metal
workers, printing
industry)
PAHs
Second Hand Smoke x Benzene
Work as a welder x Chromium VI
Dioxins
These 8 agents
constitute 85% of
all occupational
carcinogens in
Catalonia

48. Pesticides and cancer
Lindane, classified as human carcinogen (Group 1) in
relation to risk of non-Hodgkin Lymphoma (IARC 2015; D
Loomis, Lancet Oncol, 2015)
Why is there only one insecticide classified as human
carcinogen by IARC/WHO?
Lack of convincing evidence for other pesticides clearly
shows the difficulties in evaluating the carcinogenicity of
many chemical agents in human populations

49. The case of glyphosate and pressures by
industry
Letter from US congress to Dr
Collins, Director NIH calumniating
IARC and questioning NIH
funding to IARC

50. “Old problems and New methods” or is it
“New Problems and Old Methods”?
• Confounding by non-occupational exposures not a major
issue
• Major issue: Information bias (exposure misclassification)
and the problem of mixtures; need large cohort studies,
extensive exposure assessment and, in some occasions
repeated samples
• Potential major issue: selection bias, new patterns of
employment and mobility
• Uncertainty of feasibility of conducting epidemiological
research in large areas of the world

51. “Old problems and New methods” or is it
“New Problems and Old Methods”?
• Confounding by non-occupational exposures not a major
issue
• Major issue: Information bias (exposure misclassification)
and the problem of mixtures; need large cohort studies,
extensive exposure assessment and, in some occasions
repeated samples
• Potential major issue: selection bias, new patterns of
employment and mobility
• Uncertainty of feasibility of conducting epidemiological
research in large areas of the world

52. “Old problems and New methods” or is it
“New Problems and Old Methods”?
• Confounding by non-occupational exposures not a major
issue
• Major issue: Information bias (exposure misclassification)
and the problem of mixtures; need large cohort studies,
extensive exposure assessment and, in some occasions
repeated samples
• Potential major issue: selection bias, new patterns of
employment and mobility
• Uncertainty of feasibility of conducting epidemiological
research in large areas of the world

53. Prevention of Occupational Cancer
Involuntary Voluntary
Preventable
No Preventable
Involuntary + Preventable  High priority for public
health
Occupation Tobacco
Genetics Reproductive
factors

54. Estimated number and officially recognised
occupational cancers in different EU countries
(modified from Naud & Brugere 2003)
Estimated
Occ. Cancer
Recognised
Occ. Cancer
%
Recognised
France 10000 900 9%
UK 9670 806 8.3%
Germany 14700 1889 12.9%
Belgium 1850 149 8.1%
Denmark 1180 79 6.7%
Finland 890 110 12.4%
Spain 6500-13600 49 <0.1%
Datos España, Ministerio Empleo y SS, 2014

55. If It’s Not Counted It Didn’t
Happen!

56. Occupational Cancer: main messages
• Around 4% of all cancers – but varies; old exposures are
still here!
• Workplace exposures decrease in High Income and
increase in Middle Income Countries (LowIC?)
• New risks occur (or are newly identified)
• Research in occupational cancer historically very
productive; major recent findings and some failures
• Prevention of occupational cancer a global issue!

57. Thank you