Clinical trial NCT01338285: Association of Formaldehyde Exposure to Myeloid Leukemia in Workers in Guangdong, China
Official title: Studies of Myeloid Progenitor Cells in Workers Exposed to Formaldehyde, a Putative Leukemogen
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Epidemiology
Industrial Hygiene
Neoplasms
Keywords: Industry Hygiene
Molecular Epidemiology
Cancer Susceptability
Genotoxocity
FISH
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2011-04-19
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: We identified one factory that produced formaldehyde-melamine resins and one factory that used formaldehyde-melamine resins to manufacture plastic utensils. Monitoring of formaldehyde levels was performed in these factories during an initial screening and it was established that there were no other exposures to known or suspected leukemogens or hematotoxicants (e.g., benzene, phenol, chlorinated solvents). We selected a control population from three workplaces in the same @@@geographic region as factories with formaldehyde exposure and enrolled workers who had comparable demographic and socioeconomic characteristics and who were engaged primarily in manufacturing. Detailed inspection of the control workplaces did not identify potential for occupational exposure to formaldehyde or any other@@@hematotoxic or genotoxic chemicals in excess of exposure levels in the general population.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: * Subjects will be recruited from a factory that manufactures plastic utensils and that has had a stable manufacturing process for the past five years.

Primary outcomes:
measure: Hematotoxicity change
timeFrame: 2006-2034
measure: Leukemia-specific chromsome change
timeFrame: 28 years
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong National Poison Control Center (NPCC)
Study officials:
affiliation: National Cancer Institute (NCI)
name: Qing Lan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cogliano VJ, Grosse Y, Baan RA, Straif K, Secretan MB, El Ghissassi F; Working Group for Volume 88. Meeting report: summary of IARC monographs on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. Environ Health Perspect. 2005 Sep;113(9):1205-8. doi: 10.1289/ehp.7542.
citation: Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries. J Natl Cancer Inst. 2003 Nov 5;95(21):1615-23. doi: 10.1093/jnci/djg083.
citation: Egle JL Jr. Retention of inhaled formaldehyde, propionaldehyde, and acrolein in the dog. Arch Environ Health. 1972 Aug;25(2):119-24. doi: 10.1080/00039896.1972.10666147. No abstract available.