1. By : Dr. Aliraza Safaiyan M.D. Occupational Medicine Specialist Occupational Cancer

2. Introduction  One of every two or three individuals in the industrialized world will develop some type of cancer during their lifetimes  Approximately 3-10% of all human cancers are thought to be caused by occupational exposure to carcinogens  It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation  Occupational carcinogens is important because they are completely preventablee.

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

4. 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 0.4-1.1 (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.

5. 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

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

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

8. Induction-Latency period  3 - 5 years for radiation or toxin induced Leukemia  20 - 40 or more asbestos-induced Mesothelioma  Solid tumors about 10 – 12 years  For most tumors about 12 - 25 years

9. 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 InitiatorsPromoters

10. Prevention  Elimination: The most effective means is to ban the carcinogen. (asbestos).  Substitution Alternatively, 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.

11. International Agency of Research on Cancers IARC

13. 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.

14. IARC Evaluations Dimensions and Groups 14 Types of evidence Human Animal Other - mutagenicity - genotoxicity - metabolism - etc. Group 1Carcinogenic to humans 2AProbably carcinogenic to humans 2BPossibly carcinogenic to humans 3Not classifiable 4Not carcinogenic to humans

15. 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

16.  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).

21. 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.

22. 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.

23. The most Important Occupational cancers

24. Lung cancer (Exposures)  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  Inorganic arsenic  Chromium  Nickel  Mustard Gas Generalworkplaces

25. Lung cancer (findings)  Cough  Hemoptysis  Wheezing  Dyspnea  Weight loss  Anorexia  Fatigue  CXR  CT-scan  Sputum cytology  Fiberoptic Bronchoscopy  Biopsy Symptoms & SignsParaclinics

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

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

28. Mesothelioma (findings)  Chest pain  Dyspnea  Dry cough  Weight loss  Pleural effusion  Friction rub  CXR  CT-scan  Thoracentesis  Thotacotomy & thoracoscopy  Sputum cytology  SI-ADH  LDH Symptoms & signsparaclinics

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

31. Asbestos Ban (1989)

32. Bladder cancer (exposure)  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 Generalworkplace

33. Bladder cancer (findings)  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) Symptoms & signsParaclinics

34. Bladder cancer (prevention)  Avoidance of exposure  Medical monitoring : Urinary cytology (75% Sen. 99.9 Spes.)  Immunocytology

35. Liver cancer (hepatic angiosarcoma) (exposure)  Vinyl chloride  Arsenic  Copper, Lead, Zinc  Thorotrast (thorium dioxide) 1930-1955

36. Liver cancer (hepatic angiosarcoma) (findings)  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 Symptoms & singsParaclinics

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

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