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

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. 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

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

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

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

8. 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

9. International Agency of Research on Cancers IARC

10. Problems in testing  Prolonged high exposure is uncommon  Usually mix of exposures  Epi: expensive, long, past exposures, poor exposure data  Animal: high dose (Validity in humans ?! )  In vitro: mutagens, not carcinogens

11. IARC Evaluations Dimensions and Groups 11 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

12. Numbers of occupational carcinogens and high risk occupations and industries designated by the IARC Monograph Programme, 1971-2003 12 Siemiatycki et al, Environ Hlth Persp, 2004, http://www.ehponline.org MixturesOccupations Groups & Agents& Industries 1(definite) 28 12 2A(probable) 27 3 2B(possible) 113 4

13. 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

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

15. Lung cancer (prevention)  Avoidance of exposure  Medical monitoring

16. Mesothelioma (exposure)  Asbestosis (trivial contact)  Crocidolite: the most potent carcinogen

17. 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

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

20. Asbestos Ban (1989)

21. 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

22. 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

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

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

25. 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

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

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