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Occupational Cancer in the 21st century
Manolis Kogevinas MD, PhD Barcelona Institute for Global Health (ISGlobal)
[email protected]@KogevinasM
EPICOH 2017, Edinburgh
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 veryproductive; major recent findings and some failures
• Prevention of occupational cancer a global issue!
•18910 production workers and sprayers from 10 countries•4 deaths from soft-tissue sarcoma
Dioxins research: studies in workers became conclusiveonly 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 Zealandapplicators in relation to total months spent
spraying 2,4,5-T. (Smith et al, JNCI. 1992)
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.
(Doll & Peto 1981)
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)
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?)
Rubber-Tire Industry “Michelin”, England
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
Prediction of mortality from mesothelioma in England (J Peto et al., Lancet 1996)
Global Burden of Disease – Deaths and DALYs fromoccupational 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)
Occupational cancer
Present and future
Trends in occupational exposure to
carcinogens
Reduction of number of workers exposed through widerchanges in production (in Western Europe/N America) and transfer to 3rd world countries
Textiles, BangladeshC. Salgado
Ship dismantlingBangladeshC. Salgado
World mine production of asbestos from 2007 to
2012 (in 1000 metric tons)
Trends in occupational exposure to
carcinogens
Reduction of number of workers exposed through widerchanges in production (in Western Europe/N America)
More efficient control of exposure to known carcinogensin HIC through elimination, substitution, and specific and general measures of hygiene and security
Exposure to styrene among workers (laminators)
in the reinforced plastics industry, 1960-1990
Trends in occupational exposure to
carcinogens
Reduction of number of workers exposed through widerchanges in production (in Western Europe/N America)
More efficient control of exposure to known carcinogensin HIC through elimination, substitution, and specific and general measures of hygiene and security
Introduction of new materials and technologies thatcould be associated with increased risks or changes in workconditions and labour force that could have a direct orindirect association with cancer occurrence
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
Melatonin (aMT6s). Mesor (circadian mean) and acrophase(peak time) in day and night workers. Cosinor curves.
(Papantoniou, CEBP 2014)
World’s population 2017: 7 billion
(Modified from Hans Rosling)
World’s population 2100
(Modified from Hans Rosling)
Unemployment and vulnerable employment trends
and projections, 2007–18
(World Employment and Social Outlook: Trends 2017, ILO 2017)
Research in Occupational Cancer
Themes EPICOH2016 Barcelona
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 produceknowledge 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)
• The case-series phase• SMR study phase (high risks, fairly simple designs)
Phases in occupational cancer research(overlapping)
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
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
• The case-series phase• SMR study phase (high risks, fairly simple designs)• Advanced exposure assessment phase (developmentof advanced methods for exposure assessment in cohortand case-control studies)
Phases in occupational cancer research (overlapping)
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.
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
ReviewMerging
5
4
1
Mustafa Dosemeci and many others
Ana, carryingthe 63
occupationalmodular
questionnaires. EPICURO study
(Spanish bladderCancer Study)
• The case-series phase• SMR study phase (high risks, fairly simple designs)• Advanced exposure assessment phase (developmentof advanced methods for exposure assessment in cohortand case-control studies)• Molecular epidemiology phase (incorporation of molecular and omic techniques)
Phases in occupational cancer research (overlapping)
Use of mechanistic data – the case of ethylene oxide (IARC 1994)
• The case-series phase• SMR study phase (high risks, fairly simple designs)• Advanced exposure assessment phase (developmentof advanced methods for exposure assessment in cohortand 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 (withexceptions); new approaches to causal inference
Phases in occupational cancer research
Evaluations of the International Agency forResearch on Cancer (IARC) (www.iarc.fr)
• Group 1. The agent (mixture, exposurecircumstance) 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 itscarcinogenicity to humans
• Group 4. The agent is probably NOT carcinogenic to humans
Occupational Human carcinogens(Group 1- IARC)
• 118 agents in Group 1
• 57 are occupational or also occur in the occupationalenvironment (e.g. aflatoxins, SHS, radiations etc)
• Of those, 36 were identified as Group 1 before the year2000, and 21 after the year 2000
(numbers of occupational carcinogens may differ from othersummaries)
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 theyear 2000, and 28 after the year 2000
• Use of evidence on mechanisms very important forthis group (upgrade from 2B-possible to 2A-probable)
(numbers of occupational carcinogens may differ fromother summaries)
Major Occupational Human carcinogens (Group1/2A- 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
Major Occupational Human carcinogens (Group1/2A- 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 agentsconstitute 85% of all occupationalcarcinogens in Catalonia
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 clearlyshows the difficulties in evaluating the carcinogenicity of many chemical agents in human populations
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
“Old problems and New methods” or is it“New Problems and Old Methods”?
• Confounding by non-occupational exposures not a majorissue
• Major issue: Information bias (exposure misclassification) and the problem of mixtures; need large cohort studies, extensive exposure assessment and, in some occasionsrepeated 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
“Old problems and New methods” or is it“New Problems and Old Methods”?
• Confounding by non-occupational exposures not a majorissue
• Major issue: Information bias (exposure misclassification) and the problem of mixtures; need large cohort studies, extensive exposure assessment and, in some occasionsrepeated 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
“Old problems and New methods” or is it“New Problems and Old Methods”?
• Confounding by non-occupational exposures not a majorissue
• Major issue: Information bias (exposure misclassification) and the problem of mixtures; need large cohort studies, extensive exposure assessment and, in some occasionsrepeated 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
Prevention of Occupational Cancer
Involuntary Voluntary
Preventable
No Preventable
Involuntary + Preventable High priority for public
health
Occupation Tobacco
Genetics Reproductive
factors
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
If It’s Not Counted It Didn’t Happen!
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 veryproductive; major recent findings and some failures
• Prevention of occupational cancer a global issue!
Thank you