Cancer Markers Associated With Occupational Exposure to Trichloroethylene
Condition: Industrial Hygiene; Epidemiology; Neoplasms
Study type: Observational

Summary: 
      Background:

        -  Trichloroethylene (TCE) is a solvent used in many medical and industrial processes.

        -  TCE is a carcinogen (causes cancer) in rats, but its carcinogenicity in humans is
           unclear. There is some evidence of increased liver and kidney cancers and of an
           association with non-Hodgkin lymphoma in studies of workers exposed to TCE.

        -  The carcinogenicity and regulation of TCE is a matter of continuing debate.

      Objectives:

        -  To determine if TCE exposure is associated with higher levels of genetic aberrations in
           certain white blood cells called lymphocytes.

        -  To determine if TCE exposure affects lymphocyte subsets and levels of certain hormones
           called cytokines.

      Eligibility: Workers exposed to two different levels of exposure to TCE and unexposed workers
      in Guangdong Province, China.

      Design:

        -  45 workers exposed to more than 25 parts per million (ppm) TCE, 30 workers exposed to
           from 10 to less than 25 ppm TCE and 45 unexposed workers will be enrolled.

        -  Subjects wear small instruments at work that measure chemicals in the air for 1 or 2
           days during the 2-week study period. Exposed workers also wear several small skin
           patches on one of the two days.

        -  Subjects provide blood and urine samples.

        -  Subjects answer a questionnaire about work, smoking and drinking, use of medicines,
           medical history, general health, hobbies, and exposure to radiation and exposure to
           various substances at home.
    

Detailed description: 
      Trichloroethylene (TCE) is an industrial solvent used in degreasing, dry cleaning, and
      numerous other medical and industrial processes. It is a ubiquitous environmental contaminant
      of drinking water and is present in many EPA Superfund sites. TCE is a rodent carcinogen but
      its carcinogenicity in humans is unclear. There is some evidence for an elevation in liver
      and kidney cancers and somewhat more convincing evidence of an association with non-Hodgkin
      lymphoma (NHL) in epidemiological studies of occupationally exposed cohorts. Overall, the
      carcinogenicity of TCE and its regulation is a matter of continuing debate despite an
      extensive database of in vitro and in vivo animal studies and several cohort and case-control
      studies. IARC categorizes TCE as a probable human carcinogen. In order to address questions
      about TCE's potential carcinogenicity and mechanism of action in humans, we propose to
      conduct a cross-sectional study of early biologic effect biomarkers of genotoxicity and
      immunotoxicity in 45 workers exposed to greater than 25 ppm TCE, 30 workers exposed to 10-25
      ppm TCE, and 45 unexposed controls in Guangdong Province, China. We will assess TCE exposure
      level quantitatively, collect other exposure information through a questionnaire, collect
      biological samples, and assay a series of biomarkers of susceptibility, intermediate and
      early biologic effects. Our primary goal is to determine if TCE exposure increases
      chromosomal aberrations in peripheral lymphocytes, with a secondary goal of determining if
      TCE alters levels of key cytokines in plasma and changes lymphocyte subset ratios. In
      addition, our collaborators at UC Berkeley will apply a new generation of cytogenetic and
      molecular techniques to study TCE's ability to cause specific types of chromosomal
      aberrations that have been associated with NHL and related hematological malignancies as well
      as the impact of TCE on mRNA expression and the proteome. The work will compliment previous
      and ongoing OEEB studies of populations exposed to TCE and has the potential to make an
      important contribution to what little is known about the early biologic effects of TCE in
      humans.
    

Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        We carried out a cross-sectional study of workers currently exposed to TCE in the six study
        factories with TCE cleaning operations and unexposed controls. Control workers were
        enrolled from two clothes manufacturing factories, one food production factory and a
        hospital that did not use TCE and were in the same geographic region as the factories that
        used TCE. Exclusion criteria for both TCE-exposed and control workers were history of
        cancer, chemotherapy and radiotherapy, as well as previous occupations with notable
        exposure to benzene, butadiene, styrene and/or ionizing radiation.
      
Biospecimen description: 
      Plasma, Red blood cells, whole blood, cryopreserved lymphocytes, cryopreserved granulocytes,
      FISH cells, FISH slides, RNAlater, supernatant, buccal pellets, buccal slides, serum, clot,
      LeukLock, buffy coat, urine.
    
Keywords: Industry Hygiene; Molecular Epidemiology; Cancer Susceptibility; Genotoxicity; Immune Function; Cancer Susceptability