Occupational Cancers By : Dr. Aliraza Safaeian M.D. Occupational Medicine Specialist Assistant Professor of Medical School
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
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: 1) Tobacco (25 30%) 2) Diet and obesity (30 35%) 3) Infections (15 20%): HBV, HCV, HPV 4) Occupational and environmental exposure Radiation (both ionizing and non-ionizing, up to 10%) Environmental pollutants 1) Stress 2) Lack of physical activity
WHO report on Cancer Cancer is the second leading cause of death. An estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer. Approximately 70% of deaths from cancer occur in low- and middle-income countries. The total annual economic cost of cancer in 2010 was estimated at approximately US$ 1.16 trillion
WHO report on Cancer Around one third of deaths from cancer are due to the 5 leading behavioral and dietary risks: high BMI, low fruit and vegetable intake, lack of physical activity, tobacco use, and alcohol use. Tobacco use is the most important risk factor for cancer and is responsible for approximately 22% of cancer deaths.
WHO report on Cancer The most common cancers Lung (2.09 million cases) Breast (2.09 million cases) Colorectal (1.80 million cases) Prostate (1.28 million cases) Skin cancer (nonmelanoma) (1.04 million cases) Stomach (1.03 million cases) The most common causes of cancer death Lung (1.76 million deaths) Colorectal (862 000 deaths) Stomach (783 000 deaths) Liver (782 000 deaths) Breast (627 000 deaths)
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)
Introduction Carcinogen: Any chemical, physical or biologic agent present at the workplace which increases the risk of cancer among exposed workers 5-10% (3-6%) of all human cancers are thought to be caused by occupational exposure to carcinogens Occupational carcinogens is important because they are completely preventable.
The most common cancers associated with occupational exposure: lung and pleura bladder skin laryngeal nasal cavity leukemia lymphoma soft-tissue sarcomas liver
Type of Cancer Lung Bladder Mesothelioma Leukemia Laryngeal Skin Cancer (non-melanoma) Sinonasal and nasopharyngeal Kidney Liver Related to Occupational Exposure Estimated % (USA) 6.3 13 % 3 19 % 85-90% (men); 23-90% (women*) 0.8 2.8 % 1-20% (men) 1.5-6% (men) 31-43% (men) 0 2.3 % 0.4-1.1 (vinyl chloride only; men) * 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.
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
Stages in tumor development Initiation (irreversible changes in DNA) Promotion (facilitate tumor development) Progression (development to malignant tumor & metastases)
Examples (PAH) & (croton oil) in skin cancers in mice (Nitrosamine) & (PCB) in liver tumor in mice Complete carcinogens (cigarette smoke)
Initiators VS Promoters Initiators Genotoxic Carcinogenic alone Covalently bind to DNA (irreversible) Single exposure (may be) Promoters Not genotoxic Act after initiation Act by cellular proliferation (may be reversible) Repeated exposure required
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
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.
IARC International Agency of Research on Cancers
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. (Caprolactam)
IARC Evaluations Dimensions and Groups Types of evidence Human Animal Other - mutagenicity - genotoxicity - metabolism - etc. Group 1 Carcinogenic to humans 2A 2B Probably carcinogenic to humans Possibly carcinogenic to humans 3 Not classifiable 4 Not carcinogenic to humans
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
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).
Classification of the ACGIH GROUP A1: confirmed human carcinogens (group 1 of IARC and category 1A of the European Union). GROUP A2: suspected human carcinogens (group 2A of IARC and category 1B of European Union). GROUP A3: confirmed animal carcinogens with unknown relevance to humans (group 2B of IARC and category 2 of the European Union). GROUP A4: regroups agents non-classifiable as to their carcinogenicity to humans (group 3 of IARC). GROUP A5: regroups agents suspected not to be carcinogenic to humans (group 4 of IARC).
Classification of the European Union Category 1A: includes substances whose potential carcinogenicity for humans is known; classification in this category is primarily based on human data. Category 1B: includes substances whose carcinogenic potential to humans is presumed, classification in this category is primarily based on animal data. Category 2: includes substances suspected of being carcinogenic to humans. This classification is done on the basis of evidences obtained from human and/or animal studies not sufficiently convincing to place in category 1A or 1B.
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
The most Important Occupational cancers
Lung cancer (Exposures) General 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 workplaces chloromethyl ethers Polycyclic aromatic hydrocarbons (PAH) Inorganic arsenic Chromium Nickel Mustard Gas
Lung cancer (findings) Symptoms & Signs Cough Hemoptysis Wheezing Dyspnea Weight loss Anorexia Fatigue Paraclinics CXR CT-scan Sputum Cytology Fiberoptic Bronchoscopy Biopsy
Lung cancer (prevention) Avoidance of exposure Medical monitoring ( CXR, Sputum cytology )
Mesothelioma (exposure) Asbestosis (trivial contact) Crysotile, Amosite, Crocidolite, Tremolite, Anthophylite, Actinolite Crocidolite: the most potent carcinogen
Mesothelioma (findings) Symptoms & signs Chest pain Dyspnea Dry cough Weight loss Pleural effusion Friction rub paraclinics CXR CT-scan Thoracentesis Thoracotomy & thoracoscopy Sputum cytology SI-ADH LDH
Mesothelioma (prevention) OSHA PEL (1970) :5 Fiber/cm3 (1986):2 fiber/cm3 now: 0.1 fiber/cm3 Asbestos ban : since 1989 by EPA
Asbestos Ban (1989)
Bladder cancer (exposure) General 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 workplace Benzidine 2-naphthylamine Occupations in the dye, leather or rubber industry Chlornaphazine 4 chlorotoluidine Phenacetine
Bladder cancer (findings) Symptoms & signs Hematuria (Painless, gross, intermittent) 80% Vesical irritability alone 20% In advance cases: Anemia Uremia Leg edema Paraclinics Urinary cytology (in up to 75% of patients is positive) Ultrasonography Excretory urography Cystoscopy & biopsy (definitive diagnosis)
Bladder cancer (prevention) Avoidance of exposure Medical monitoring : Urinary cytology (75% Sen. 99.9 Spes.) Immunocytology
Liver cancer (hepatic angiosarcoma) (exposure) Vinyl chloride Arsenic Copper, Lead, Zinc smelting Thorotrast (thorium dioxide) 1930-1955
Liver cancer (hepatic angiosarcoma) (findings) Symptoms & sings Asymptomatic (some time) RUQ abdominal pain Weight loss Fatigue Hepatomegaly with ascitis Jaundice Splenomegaly Paraclinics Ultrasonography Radionuclide liver scan Hepatic angiography Liver biopsy (hemorrhage) Lab data: Mild anemia (target cell & schistocyt), Leukocytosis, thrombocytopenia LFT LDH
Liver cancer (hepatic angiosarcoma) (prevention) Avoidance of exposure Medical monitoring (history, Ph/E, CBC, LFT, Ultrasonography)
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