occupational cancer

OCCUPATIONAL CANCER Professor E.E.U. Akang

OCCUPATIONAL HEALTH UNIT, DEPT. OF PREVENTIVE MEDICINE & PRIMARY CARE, COLLEGE OF MEDICINE,

UNIVERSITY OF IBADAN2011/2012 ACADEMIC CALENDAR

MPH (OH) 0HS 70224 October 2012

Lecture Outline

• Definitions (Cancer, Occupational cancer)• Epidemiological considerations• Carcinogenesis- basic principles• Classes (IARC groups) of carcinogens• Strategies for identification of carcinogens• Primary prevention of occupational cancer• Topical issues• Closing remarks

What is cancer?• A malignant (“potentially lethal”) neoplasm

(“new growth”) that invades normal tissues and spreads (metastasises) to distant sites

• Neoplasms are growths resulting from clonal proliferation of cells following progressive accumulation of hereditary and acquired insults resulting in mutations of genes that control cell proliferation and cell death

What is occupational cancer?• Cancer specifically attributed to significant

levels of exposure to an agent* in the workplace and occurring among substantial numbers of workers.

• Substantial: > 10,000 workers

• Significant: As much as, or more than, in the general environment

*An agent that has been causally linked with development of cancer is called a carcinogen

Siemiatycki et al, Environ Hlth Persp, 2004, http://www.ehponline.org

Lecture Outline


What is the global and national burden of cancer?

• 5 million female and 6 million male new cancer cases worldwide (of which 100,000 occur in Nigeria) annually

• >6 million deaths worldwide annually• >50% of patients with cancer live in developing

countries, which have <10% of the resources for cancer therapy

Global statistics on cancer, 2002

What is the global burden of occupational cancer?

• POPULATION ATTRIBUTABLE FRACTION (RISK PER CENT)

This is defined as the fraction (percentage) of the diseased persons in the population whose disease would have been prevented had the exposure been absent

In the case of occupational cancers, a crude estimate for this percentage is between 2-10%

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What is the relevance of occupationalcancer epidemiology?

1. 50% of known human carcinogens are substances found principally in the workplace

2. Many cases of cancer are directly attributable to occupational exposure

3. Control measures can often be implemented once an occupational carcinogen has been identified

4. The discovery of occupational carcinogens has importance outside the factory walls

5. Provides a basis for compensating victims6. Improves our understanding of carcinogenesis

Siemiatycki et al, Environ Hlth Persp, 2004, http://www.ehponline.org

Lecture Outline


What do we know about carcinogenesis in general?

Carcinogenesis is a multi-hit, multi-stage processResults from the cumulative effect of repeated prolonged exposure to environmental carcinogens in concert with inherent genetic/other susceptibility•>80% NATURE- environment- <10% NURTURE- genesRadiation, Chemicals, Viruses60% of all cancers are PREVENTABLECarcinogens may be 1. Genotoxic (interact with and alter DNA)2. Epigenetic (affect gene expression)

Historical landmarks• 1775, Percivall Pott in London- scrotal cancer

among chimney sweeps• 1895, Rehn, in Germany- cluster of three cases of

bladder cancer in workers at a local factory producing aniline dyestuffs from coal tar

• Early 20th century- certain constituents of tar, soot, and oils, known as polycyclic aromatic hydrocarbons, were found to cause cancer in laboratory animals

• 1970, IARC recommended that a compendium on carcinogenic chemicals be prepared by experts

What do we know about occupational carcinogens?- 1

Exposure may be acquired via1 INHALATIONaverage concentration of the substance in the breathing zone over a reference period (8 hours for long-term, and 15 minutes for short-term exposure)2 DERMAL CONTACTpotential dose rate predominantly to the hands and forearms (2000 cm2) is calculated using a mathematical model3 INGESTIONnot quantifiable

What do we know about occupational carcinogens?- 2

Occupationally related cancers are characterized by a long latent period—time between first exposure and clinical presentation (usually >10-15 years) and up to 40-50 years in some cases (i.e. presentation can be in retirement rather than while still at work).

An occupationally related tumour does not differ substantially, either pathologically or clinically, from its “naturally occurring” counterpart.

Lecture Outline


IARC classes of carcinogens

On the basis of epidemiological, animal and in vitro experimental studies, occupational agents linked with cancer have been categorised into 4 major groups by the IARC

1 Carcinogenic to humans (21%)2A Probably carcinogenic to humans (16%)2B Possibly carcinogenic to humans (63%)3 Not classifiable4 Not carcinogenic to humans

GROUP 1 (DEFINITE)CARCINOGENS40% (40) IARC group 1 carcinogens are occupational. Others include radiation, viruses and lifestyle factorsPHYSICAL AGENTS ASSOCIATED CANCERS

Ionizing radiation Breast cancer, leukaemia, skin cancer

Unltraviolet light Skin cancer

Asbestos Lung cancer, mesothelioma

CHEMICAL AGENTS ASSOCIATED CANCERS

Arsenic Skin cancer, lung cancer

Vinyl chloride Liver angiosarcoma

Aromatic amines Bladder cancer

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IARC Group 1 occupations and industries

Aluminium production Haematite mining

Auramine Iron and steel founding

Boot and shoe Isopropanol

Coal gasification Magenta

Coke production Painter

Furniture & cabinet making Rubber industry

GROUP 2A (PROBABLE) CARCINOGENS30 IARC group 2A carcinogens are occupational. CHEMICAL AGENTS ASSOCIATED CANCERS

Polyaromatic hydrocarbons Lung, bladder & skin cancer

Wood & Fossil fuel products Skin cancer

Plastic & rubber byproducts Bladder cancer

Chlorinated hydrocarbons Several cancers

Inorganic lead compounds Lung cancer

Aromatic amine dyes (e.g. benzidine-based dyes)

Bladder cancer

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IARC Group 2A occupations and industries

• Art glass manufacturing

Cobalt metal manufacturing

Hairdresser or barber

Petroleum refining

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IARC Group 2B occupational carcinogens

• Refractory ceramic fibres• Nickel alloys• Carbon black• Gasoline engine exhaust• Gasoline• Bitumens

• Styrene• Acrylonitrile• Chloroform• Dichloromethane• Some pesticides• Welding fumes

117 IARC group 2B carcinogens are occupational.

Lecture Outline


Strategies for discovering occupational carcinogens

• Epidemiological surveys• Animal experimentation (toxicological studies)• Other experimental studies Ames mutagenicity test (Salmonella, E. coli)Mammalian in vitro mutagenicity test (Chinese

hamster lung derived cells)Mouse in vivo clastogenicity assay

Lecture Outline


Primary prevention of occupational cancer

• Recognition of hazards and risks• Education of management and workforce• Elimination of exposure (substitution,

automation)• Reduction of exposure• Provision of personal protective equipment• Limiting access• Adequate facilities for showering, changing, etc.• Legislative provisions

Veys, 1996, http://dx.doi.org/10.1136/bmj.313.7057.615

Lecture Outline


Topical issues in occupational cancer

•May be a significant and under estimated problem in developed and developing countries•Challenges include exposure assessment, sample size, confounding factors, manpower to conduct research, ethical issues, legislation (particularly in developing countries)•Confounding factors include age, social class, “healthy worker” effect•Interaction- different joint effect of 2+ carcinogens (i.e. synergy (multiplicative) and antagonism)

Lecture Outline


Closing remarks• Occupational cancer affords significant

opportunities for research• Cancers related to the workplace can be

reduced by the implementation of primary prevention and by increased vigilance of occupational health workers

• Advocacy is essential to raise awareness of general public, legislators, employers and workers

THANKS FOR LISTENING!

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A little learning is a dang'rous thing;Drink deep, or taste not the Pierian

spring.Alexander Pope