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DCEG Research on Formaldehyde Exposure

Researchers in the Occupational and Environmental Epidemiology Branch (OEEB) have been conducting studies of occupational formaldehyde exposure and cancer risk since the 1980s. Early studies focused on surveys of professionals who are potentially exposed to formaldehyde in their work, such as anatomists and embalmers (Walrath and Fraumeni, 1983; Walrath and Fraumeni, 1984; Stroup et al., 1986; Hayes et al., 1990). Although these early studies reported that these professionals were at increased risk for leukemia compared to the general population, they did not evaluate specific exposures or work practices. More recently, OEEB scientists conducted a study investigating the relationship between work practices and formaldehyde exposure with risk for selected malignancies among workers in the funeral industry. Occupational histories were obtained from next of kin and co-workers for cases of lymphohematopoietic malignancies (n=167) and for a control group of deaths due to other causes. Risk of death from myeloid (n=34) but not other types of leukemia, was increased among those whose peak exposure to formaldehyde was highest. There was also evidence that greater than average levels of exposure to formaldehyde in these jobs was related to risk of death from myeloid leukemia (Hauptmann et al., 2009).

In the NCI Formaldehyde Industrial Cohort study, which began in the 1980s and includes 25,619 workers in industries with potential formaldehyde exposure, OEEB scientists estimated exposure based on work histories and plant-specific measurement data. In the most recent publication from this cohort that focused on deaths from lympohematopoietic malignancies, a possible link between formaldehyde exposure and lymphohematopoietic malignancies, particularly myeloid leukemia (n=48), was observed with peak exposure. When cumulative risk was evaluated, risks declined steadily over time, such that the cumulative excess risk of myeloid leukemia was no longer statistically significant at the end of the follow-up period. Similar to patterns of risk over time seen for known leukemogens, the risk for myeloid leukemia appeared to be highest earlier in the follow-up period. By the end of the follow-up period, the risk was no longer statistically significant (Beane Freeman et al., 2009). Formaldehyde exposure was also associated with increased risk of death from nasopharyngeal cancer, a rare malignancy. No association with lung cancer was observed in this update of the cohort (Beane Freeman et al., 2013).

Biologic Plausibility for Leukemia

In the first chromosome wide association study (CWAS) using cultured myeloid progenitor cells from workers exposed to formaldehyde, there was an increase in monosomy and trisomy of multiple chromosomes and an increase in structural chromosomal aberrations of chromosome 5 (Lan et al., 2015), which are often present in acute myeloid leukemia. Formaldehyde exposure was also associated with a decrease in levels of CD8+ effector memory T cells and regulatory T cells (Hosgood et al., 2013).

Results from these studies have been cited in several reviews on the carcinogenicity of formaldehyde including those conducted by the International Agency for Research on Cancer and the National Toxicology Program Report on Carcinogens Outside Expert Panel.

For more information, contact Laura Beane-Freeman.

Occupational and Environmental Epidemiology Branch - Research Areas

NCI’s Fact Sheet on Formaldehyde and Cancer Risk

DCEG Formaldehyde Study Publications