1. Occupational Cancers By : Dr. Aliraza Safaeian M.D.
Occupational Medicine Specialist
Assistant Professor of Medical School

2. Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body
Over 100 types of cancers affect humans

3. Causes
90–95% of cases, are due to genetic mutations from environmental factors
5–10% are due to inherited genetics
Common environmental factors that contribute to cancer death:
Tobacco (25–30%)
Diet and obesity (30–35%)
Infections (15–20%): HBV, HCV, HPV
Occupational and environmental exposure
Radiation (both ionizing and non-ionizing, up to 10%)
Environmental pollutants
Stress
Lack of physical activity

4. In 2015, about 90.5 million people had cancer.
About 14.1 million new cases occur a year (not including skin cancer other than melanoma)
If skin cancer other than melanoma were included in total new cancers each year, it would account for around 40% of cases.
It caused about 8.8 million deaths (15.7% of deaths).

5. The most common types of cancer
In males:
lung cancer, prostate cancer, colorectal cancer and stomach cancer.
In females:
breast cancer, colorectal cancer, lung cancer and cervical cancer.
In children:
ALL, brain tumors, non-Hodgkin lymphoma (in Africa)

6. Introduction
Carcinogen: Any chemical , physical or biologic agent present at the workplace which increases the risk of cancer among exposed workers
5-10% of all human cancers are thought to be caused by occupational exposure to carcinogens
Occupational carcinogens is important because they are completely preventable.

7. The most common cancers associated with occupational exposure:
lung and pleura
bladder
skin
laryngeal
nasal cavity
leukemia
lymphoma
soft-tissue sarcomas
liver

8. Related to Occupational Exposure Estimated % (USA)
Type of Cancer
6.3 – 13 %
Lung
3 – 19 %
Bladder
85-90% (men);  23-90% (women*)
Mesothelioma
0.8 – 2.8 %
Leukemia
1-20% (men)
Laryngeal
1.5-6% (men)
Skin Cancer (non-melanoma)
31-43% (men)
Sinonasal and nasopharyngeal
0 – 2.3 %
Kidney
(vinyl chloride only; men)
Liver
* In general, the overall attributable risk for mesothelioma in women is 23%. However, if the woman has had "take-home" exposure to asbestos, the risk may be around 90%. "Take-home" exposure results from asbestos being carried home on contaminated work clothing or other items.

9. Risk of developing a particular cancer
Personal characteristics such as age, sex, and race
Family history of cancer
Diet and personal habits such as cigarette smoking and alcohol consumption
The presence of certain medical conditions
Exposure to cancer-causing agents in the environment
Exposure to cancer-causing agents in the workplace

10. Stages in tumor development
Initiation (irreversible changes in DNA)
Promotion (facilitate tumor development)
Progression (development to malignant tumor & metastases)

11. Examples (PAH) & (croton oil) in skin cancers in mice
(Nitrosamine) & (PCB) in liver tumor in mice
Complete carcinogens (cigarette smoke)

12. Initiators VS Promoters
Genotoxic
Carcinogenic alone
Covalently bind to DNA (irreversible)
Single exposure (may be)
Not genotoxic
Act after initiation
Act by cellular proliferation (may be reversible)
Repeated exposure required

13. Induction-Latency period
3 - 5 years for radiation or toxin induced Leukemia
or more asbestos-induced Mesothelioma
Solid tumors about 10 – 12 years
For most tumors about years

14. Prevention
Elimination: The most effective means is to ban the carcinogen. (asbestos).
Substitution: a carcinogenic substance may be substituted with one that is not carcinogenic, or is less hazardous.
Engineering controls: (expensive, but effective means) for example, ventilation, enclosure or partial enclosure, isolation
Administrative controls: job rotation
Personal protective equipment (PPE): is the least efficient way of controlling hazardous exposures.

15. International Agency of Research on Cancers
IARC
International Agency of Research on Cancers

17. the IARC classifications
Group 1: The agent is carcinogenic to humans. sufficient evidence of carcinogenicity in humans.
Group 2A: The agent is probably carcinogenic to humans. limited evidence of carcinogenicity in humans and sufficient evidence in experimental animals.
Group 2B: The agent is possibly carcinogenic to humans. limited evidence of carcinogenicity in humans and less than sufficient evidence in experimental animals.
Group 3: The agent is not classifiable as to its carcinogenicity to humans. the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals.
Group 4: The agent is probably not carcinogenic to humans. there is evidence suggesting lack of carcinogenicity in humans and in experimental animals.

18. IARC Evaluations Dimensions and Groups
Types of evidence
Human
Animal
Other
- mutagenicity
- genotoxicity
- metabolism
- etc.
Group
1 Carcinogenic to humans
2A Probably carcinogenic
to humans
2B Possibly carcinogenic
3 Not classifiable
4 Not carcinogenic

19. the IARC classifications
Group 1 : 63 agents, 13 mixtures and 15 exposure circumstances. This includes a number of occupations (eg painter, cabinet maker) as well as different chemicals used primarily in occupational circumstances.
group 2A : 31 agents and 3 exposure circumstances are classified.
Not all these agents are occupational carcinogens and a review of the IARC classifications found that 28 agents were definite occupational carcinogens, and a further27 were probable occupational carcinogens

20. Occupational Carcinogens
28 definite human occupational carcinogens (IARC group 1);
• 27 probable human occupational carcinogens (IARC group 2A);
• 113 possible human occupational carcinogens (IARC group 2B); and
• 18 occupations and industries that possibly, probably or definitely
entail excess risk of cancer (IARC groups 1, 2A and 2B).

25. United States Department of Health and Human Services Report on Carcinogens (RoC)
Substances on the RoC are classified into one of two groups: • Known to be human carcinogen. • Reasonably anticipated to be human carcinogenic. The 10th RoC classifies 52 substances into the known carcinogens group, and a further 176 substances into the reasonably anticipated carcinogens group.

26. United States Environmental Protection Authority (EPA)
Agents can be classified as:
• Carcinogenic to humans: when there is convincing epidemiologic evidence demonstrating causality between human exposure and cancer.
• Likely to be carcinogenic to humans: when the available data are adequate to demonstrate carcinogenic potential to humans.
• Suggestive evidence of carcinogenic potential: when the evidence from human or animal data is suggestive of carcinogenicity but is not sufficient for a stronger conclusion.
• Inadequate information to assess carcinogenic potential.
• Not likely to be carcinogenic to humans.
the EPA are much more conservative than any other organization. They have only classified three substances (arsenic, benzene, chromium IV) as carcinogenic to humans, and a further 102 as likely or probable carcinogens. They have not evaluated any form of asbestos.

27. Avoid the use of chemical in IARC groups 1 and 2A
Use agent in group 2B only with very tight controls when there are no viable alternatives

28. The most Important
Occupational cancers

29. Lung cancer (Exposures)
General
workplaces
Tobacco smoking is responsible for nearly 90% of all lung cancers.
Second-hand smoke
Byproducts of fossil fuel
Air pollution
Insufficient consumption of fruits and vegetables
High doses of ionizing radiation
Asbestos
Radon
chloromethyl ethers
Polycyclic aromatic hydrocarbons (PAH)
Inorganic arsenic
Chromium
Nickel
Mustard Gas

30. Lung cancer (findings)
Symptoms & Signs
Paraclinics
Cough
Hemoptysis
Wheezing
Dyspnea
Weight loss
Anorexia
Fatigue
CXR
CT-scan
Sputum Cytology
Fiberoptic Bronchoscopy
Biopsy

31. Lung cancer (prevention)
Avoidance of exposure
Medical monitoring ( CXR , Sputum cytology )

32. Mesothelioma (exposure)
Asbestosis (trivial contact)
Crysotile, Amosite, Crocidolite, Tremolite, Anthophylite, Actinolite
Crocidolite: the most potent carcinogen

33. Mesothelioma (findings)
Symptoms & signs
paraclinics
Chest pain
Dyspnea
Dry cough
Weight loss
Pleural effusion
Friction rub
CXR
CT-scan
Thoracentesis
Thoracotomy & thoracoscopy
Sputum cytology
SI-ADH
LDH

35. Mesothelioma (prevention)
OSHA PEL (1970) :5 Fiber/cm3
(1986):2 fiber/cm3
now: 0.1 fiber/cm3
Asbestos ban : since 1989 by EPA

36. Asbestos Ban (1989)

37. Bladder cancer (exposure)
General
workplace
The most important risk factor is cigarette smoking .
Heavy coffee consumption (Possible risk factors )
Bladder infection with schistosoma
Cyclophosphamide
Long-term use of pain killers containing phenacetin,
Urinary tract infections or low urine flow
Genetic factors
Benzidine
2-naphthylamine
Occupations in the dye, leather or rubber industry
Chlornaphazine
4 chlorotoluidine
Phenacetine

38. Bladder cancer (findings)
Symptoms & signs
Paraclinics
Hematuria (Painless, gross, intermittent) 80%
Vesical irritability alone 20%
In advance cases:
Anemia
Uremia
Leg edema
Urinary cytology (in up to 75% of patients is positive)
Ultrasonography
Excretory urography
Cystoscopy & biopsy (definitive diagnosis)

39. Bladder cancer (prevention)
Avoidance of exposure
Medical monitoring :
Urinary cytology (75% Sen Spes.)
Immunocytology

40. Liver cancer (hepatic angiosarcoma) (exposure)
Vinyl chloride
Arsenic
Copper, Lead, Zinc smelting
Thorotrast (thorium dioxide)

41. Liver cancer (hepatic angiosarcoma) (findings)
Symptoms & sings
Paraclinics
Asymptomatic (some time)
RUQ abdominal pain
Weight loss
Fatigue
Hepatomegaly with ascitis
Jaundice
Splenomegaly
Ultrasonography
Radionuclide liver scan
Hepatic angiography
Liver biopsy (hemorrhage)
Lab data:
Mild anemia (target cell & schistocyt), Leukocytosis, thrombocytopenia
LFT
LDH

42. Liver cancer (hepatic angiosarcoma) (prevention)
Avoidance of exposure
Medical monitoring (history, Ph/E, CBC, LFT, Ultrasonography)

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