Symptoms and General Pathology

All Conditions

Rare Diseases

Disease Susceptibility

Chromosome Aberrations

Oculocerebral Syndrome With Hypopigmentation

Qing Lan, M.D.

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.

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.

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.

Cancer Markers Associated With Occupational Exposure to Trichloroethylene

A Cross-Sectional Study of Occupational Exposure to Trichloroethylene, Chromosomal Aberrations, and Related Biomarkers in Guangdong, China

The primary goal of the study is to determine if TCE exposure is associated with higher levels of chromosomal aberrations in peripherallymphocytes. The additional goals of the study, to be funded by extramural collaborators, are to evaluate TCE urinary metabolite patterns, alterations in specific types of chromosomal aberrations that have been detected in NHL and other hematopoietic malignancies, and alterations in mRNA expression and the proteome.

A secondary goal of the study is to determine if TCE exposure alters plasma cytokine levels and lymphocyte subsets.

National Cancer Institute (NCI)

Neoplasms

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Myeloid Leukemia

Anti-Infective Agents

All Drugs and Chemicals

Formaldehyde

Workers exposed to high levels of formaldehyde and unexposed workers in Guangdong Province, China.

Background:

* Research suggests that occupational exposure to formaldehyde is associated with increased risk for myeloid leukemia, but the significance of these findings is uncertain because of inconsistencies among studies and lack of knowledge of how formaldehyde can cause leukemia.
* Damage to the DNA of myeloid cells (type of white blood cell) or an environmental factor not affecting the cell genetic machinery may be involved.

Objective: To determine if formaldehyde exposure is associated with genetic or other changes in myeloid cells.

Eligibility: Workers exposed to high levels of formaldehyde and unexposed workers in Guangdong Province, China.

Design:

* 40 exposed workers and 40 unexposed workers will be enrolled.
* Subjects wear small instruments at work that measure chemicals in the air for 1 or 2 days.
* Subjects have a brief physical examination and provide blood, urine, and mouth rinse samples.
* Subjects answer a questionnaire about work, smoking and drinking, use of medicines, medical history, general health, exposure to radiation and exposure to various substances at home.

Research in industrial workers and professionals exposed to formaldehyde suggests that occupational exposure to this important chemical is associated with increased risk for myeloid leukemia. The significance, however, of these observations for occupational and environmental health is uncertain because of inconsistencies among epidemiologic studies and lack of a demonstrated mechanism through which formaldehyde can cause leukemia. Cytogenetic damage is one potential leukemogenic mechanism, but there are few studies of formaldehyde-exposed humans. Some experimental data suggest that epigenetic changes in myeloid cells could also be involved. We plan to study 40 workers exposed to high levels of formaldehyde and 40 unexposed controls to examine the hypothesis that formaldehyde is associated with these changes. To determine formaldehyde exposure, we will incorporate a number of methods, including questionnaires to determine potential past exposure and on-site monitoring to determine current average and peak intensities of exposure. We will then examine differences in aneuploidy and structural abnormalities in myeloid progenitor cells cultured from peripheral blood. We will specifically look for differences in genes associated with myeloid leukemia such as monosomy 7 and trisomy 8 using interphase and Octochrome FISH. We will also determine whether aberrant methylation in progenitor cells, specifically hypermethylation of genes associated with myeloid leukemia, is higher in those exposed to formaldehyde. This study will substantially contribute to our understanding of the leukemogenic potential of formaldehyde, which has important public health and regulatory implications.

Association of Formaldehyde Exposure to Myeloid Leukemia in Workers in Guangdong, China

Studies of Myeloid Progenitor Cells in Workers Exposed to Formaldehyde, a Putative Leukemogen

This study will determine if formaldehyde is associated with epigenetic changes in myeloid progenitor cells, including global methylation and hypermethylation in genes that have been linked to myeloid leukemia (ML) such as p15, HIC1, ER, CDH1 and ABL.

This study will determine if formaldehyde exposure is associated with aneuploidy in myeloid progenitor cells using interphase-FISH, with a particular focus on monosomy of chromosome 7 and aneuploidy of other relevant chromosomes, such as trisomy 8; and if formaldehyde exposure is associated with increased levels of structural aberrations relevant for myeloid leukemogenesis \[e.g., 5q-\] in myeloid progenitor cells using OctoChrome FISH, which will evaluate aberrations in all 24chromosomes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Cancer Markers Associated With Occupational Exposure to Trichloroethylene	NCT00481611	Industrial Hygi... Epidemiology Neoplasms		18 Years - 50 Years	National Institutes of Health Clinical Center (CC)
Association of Formaldehyde Exposure to Myeloid Leukemia in Workers in Guangdong, China	NCT01338285	Epidemiology Industrial Hygi... Neoplasms		18 Years - 50 Years	National Institutes of Health Clinical Center (CC)

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