Document Sample

    Jay Harper, MD, MPH
• 2 to 8 % of all cancers are thought to be
  due to occupational exposures (Doll &
• Prevention is key
• Environmental as well as occupational
• Multifactorial
• 1775: Sir Percival Pott: scrotal cancer in
  chimney sweeps
• 1895: Bladder cancer: aromatic amines
• 1973: Lung cancer: bis-chloromethylether
• 1974: Liver angiosarcoma: vinyl chloride
  Stages of Tumor Development
• Initiation
  – Active mutation or damage to DNA
  – Single exposure may be sufficient
    (carcinogenic by themselves)
  – Action is irreversible
  – No apparent threshold
  – No morphologic changes in initiated cell
  – Dependency on metabolism and the cell cycle
 Stages of Tumor Development
• Promotion
  – May speed cell production or suppress
  – Causes morphologic changes
  – Modulation by environment and lifestyle
  – Probable threshold
  – Reversible
  Stages of Tumor Development
• Progression
  – Additional changes necessary for the
    development of a malignant tumor
     • Likely triggered by genetic events
  – Development of invasiveness, metastasis,
    irreversible changes in genome
  – If no progression, then remains at benign stage
    such as papilloma, nodules or adenoma
     Criteria for Causality
• STRENGTH – magnitude of relative risk
• CONSISTENCY – reported in multiple
  studies with different circumstances
  response validity
• TEMPORALITY – cause precedes effect
• Advantages
  – Allows direct assessment in humans
  – May detect cancer cluster
  – Allows observation of cumulative effects of
    environmental and lifestyle factors affecting
    various stages
  – Allows estimates of relative risk
• Disadvantages
  – Long latency periods
  – Limited to those materials used for many years
  – Retirement of workers
  – Difficulty with small risk: extrapolation
    beyond available data, poor-exposure record
    keeping, poor exposure recall, worker job
  – Confounding risk factors cannot be controlled
               Animal Studies
•   IARC requirements
•   Good qualitative predictor
•   Not-so-good quantitative predictor
•   Limitations
    – High dose exposure is needed in order to detect
    – Different metabolism
    – Different routes of administration
         Short - Term Tests
• Provide evidence of mutagenicity
• Ames test, sister-chromatin exchange, DNA
• Quicker results, less expensive
• Correlation of results with animals/humans
         Molecular Biology
• Allows assessment of exposure and possible
  early health effects
• Measure enzyme activity of the cytochrome
  p450 monooxygenase class
• Measurement of DNA or protein adducts
• Measurement of protein products in the
           Regulatory Issues
• If there is sufficient evidence of
  carcinogenicity, then corrective action is
  taken, even if uncertainty exists
• Limited evidence should be stimulus for
  more research
• Risk assessment is crucial to best public
• IARC: International Agency for Research
  on Cancer
• ACGIH: American Conference of
  Governmental Industrial Hygienists
• NTP: US Public Health Service National
  Toxicology Program
• NIOSH: National Institute for Occupational
  Safety and Health
• Group 1 – carcinogenic to humans
• Group 2
  – 2A – probably carcinogenic to humans
  – 2B – possibly carcinogenic to humans
• Group 3 – not classifiable
• Group 4 – probably not carcinogenic to
     Known Human Occupational
           Lung Cancers
•   Arsenic               •   Coal-related products
•   Asbestos              •   Mustard gas
•   Beryllium             •   Nickel
•   Cadmium               •   Radon
•   Chloromethyl ethers   •   Vinyl chlorine
•   Chromium
       Lung Cancer - Asbestos
• Chrysotile is the most common form of asbestos
  (Other forms are amosite, crocidolite, tremolite)
• Asbestos affects parenchyma and pleura of lungs
• Can cause cancer of larynx, GI tract (stomach) as
  well as lung
• Long latency
• Synergism with smoking
     Asbestos - Mesothelioma
• Uncommon
• No evidence for direct relationship
• Dose – response relationship exists,
  although no threshold theorized
• No interaction with smoking
• All fiber types may cause mesothelioma
  – Crocidolite (long, thin fiber) is the most potent
   Lung Cancer - Chloromethyl
• Chloromethyl methyl ether (CMME) and
  Bis (chloromethyl) ether (BCME)
• BCME more potent then CMME
• Oat cell type
• Intermediate product used in ion-exchange
  resins, bactericides, pesticides and solvents
     Lung Cancer - Chromium
• Hexavalent (+6) form is carcinogenic; other
  forms are not
• Also causes perforated nasal septum
• Used as hardening agent in metallic
         Lung Cancer - Arsenic
• May cause skin cancer, as well as lung cancer
• Synergistic with smoking
   – Between additive and multiplicative
• Most often seen in upper lobes
• Copper smelting and pesticide production
• Found in natural and man-made sources
   – Seafood source is non-toxic
   – Toxic in Fowler’s solution (used for eczema/psoriasis)
     and pesticides (vineyard workers)
        Lung Cancer - Nickel
• Associated with lung, nasal and laryngeal
• Nickel mining and refining
• Soluble forms are more potent
• Squamous cell most common type
• Good housekeeping is especially important
  for reducing occupational exposure
    Lung Cancer - Coal-related
• PAH – Polyaromatic Hydrocarbon
• Known carcinogens are benz(a)anthracene and
  7,12 dimethylbenzanthracene
• Lung cancer is seen in coke-oven workers; scrotal
  cancer in chimney sweeps
• PAH’s are formed through incomplete combustion
  of coal, tar, coke and oil
• PAH’s found in coal gasification facilities, gas and
  coke works, iron and steel foundries, petroleum
  distillates and diesel exhaust.
      Lung Cancer - Mustard Gas
•   Bis (beta-chloroethyl) sulfide
•   Poisonous gas used in WWI
•   Causes squamous cell lung CA
•   Excess lung cancers seen in Japanese and
    German workers manufacturing mustard
        Lung Cancer - Radon
• “Wasting disease of the mountains” seen in
  miners by Agricola and Paracelsus
• Radon daughter products
• Cigarette smoking acts synergistically with
• Lifetime dose in certain dwellings is
Prevention of Occupational Lung
• Primary prevention is important
  – Smoking cessation
• Secondary prevention (medical monitoring)
  – OSHA mandates monitoring for asbestos,
    acrylonitrile, arsenic, silica, and vinyl chloride
  – NIOSH recommends monitoring for beryllium,
    carbon black, chromium VI, coal tar products,
    inorganic nickel and coal gasification
  – Chemopreventive agents
    Upper Respiratory Cancers
• Sino-nasal
  – Nickel, wood dust, chromium , cutting oils,
    mustard gas
• Laryngeal
  – Asbestos, nickel, mustard gas, cutting oils
          Hematologic Cancers
• Risk Factors
  –   Ionizing radiation
  –   Benzene
  –   Agricultural work
  –   Cytotoxic drugs
 Hematologic Cancer - Ionizing
• Studies from atomic blasts from WWII
• Associated with all leukemia types except
• ALARA (as low as reasonably achievable)
 Hematologic Cancer - Benzene
• Associated with pancytopenia and AML
• Industrial rubber workers, refinery workers,
  chemical workers (soaps, dyes, cosmetics,
  perfumes), explosives industry
• Safe exposure level unknown
        Hematologic Cancer -
        Agricultural Exposure
• Farmers
• Multiple etiologies, including pesticides and
• Leukemia, Multiple Myeloma, Hodgkin’s
  Disease and Non-Hodgkin’s Lymphoma
  Hematologic Cancer - Medical
• Anti-neoplastic drugs
• Ethylene oxide
• Radiation
             Bladder Cancer
• Especially dye/pigments and tire/rubber mfg.
• Up to 20% of bladder CA related to occupation
• Kidney concentrates toxin; prolonged exposure in
• Benzidene
• 2-Naphylamine
• 4-Nitrobiphenyl
• 4,4-methylene-bis-(2-chloroaniline) or MOCA
• 4,4-methylene dianiline or MDA
     Bladder Cancer Screening
• Hematuria – high risk populations only
• Urine cytology
• Newer areas of detection: quantitative
  fluorescence image analysis (QFIA) and
  DNA flow cytometry.
• Sensitivity/specificity issues
    Bladder Cancer Screening
• NIOSH recommendations
  – Screening for bladder cancer should be viewed
    as a research endeavor whose benefits are not
    yet delineated
  – Screening techniques are evolving; it would be
    wise to bank serum and urine samples
  – Natural history of bladder CA is unclear, thus
    the value of detecting superficial versus
    invasive lesions is unclear
                  GI Tract
• Gastric
  – Asbestos, wood dust, rubber industry
• Colon
  – Sedentary work is risk factor
  – Asbestos and rubber industry suspected
  – Screening (Digital Rectal Exam vs. stool guiac
    vs. sigmoidoscopy)
              GI Tract - Liver
•   Hepatitis B&C, alcohol, aflatoxins
•   Asbestos suspected
•   Solvents associated with hepatic fibrosis
•   Hepatic Angiosarcoma
    – Vinyl chloride
    – Thorotrast
    – Arsenic
               Skin Cancer
•   Ionizing radiation
•   Arsenic
•   Polycyclic aromatic hydrocarbons
•   UV radiation

Lingjuan Ma Lingjuan Ma MS
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