Occupational Cancer in the 21st century

Manolis Kogevinas MD, PhD Barcelona Institute for Global Health (ISGlobal)

manolis.kogevinas@isglobal.org@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