Journal of the National Cancer Institute Advance Access originally published online on May 12, 2009
JNCI Journal of the National Cancer Institute 2009 101(10):751-761; doi:10.1093/jnci/djp096
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Mortality From Lymphohematopoietic Malignancies Among Workers in Formaldehyde Industries: The National Cancer Institute Cohort
Affiliations of authors: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD
Correspondence to: Laura E. Beane Freeman, PhD, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, EPS/8112 Rockville, MD 20892 (e-mail: freemala{at}mail.nih.gov).
Background: Formaldehyde exposure is associated with leukemia in some epidemiological studies. In the National Cancer Institute’s formaldehyde cohort, previously followed through December 31, 1979, and updated through December 31, 1994, formaldehyde exposure was associated with an increased risk for leukemia, particularly myeloid leukemia, that increased with peak and average intensity of exposure.
Methods: We extended follow-up through December 31, 2004 (median follow-up = 42 years), for 25 619 workers employed at one of 10 formaldehyde-using or formaldehyde-producing plants before 1966. We used Poisson regression to calculate relative risk (RR) estimates and 95% confidence intervals (CIs) to examine associations between quantitative formaldehyde exposure estimates (peak exposure, average intensity and cumulative exposure) and death from lymphohematopoietic malignancies. All statistical tests were two-sided and considered to be significant at P = .05.
Results: When follow-up ended in 2004, there were statistically significant increased risks for the highest vs lowest peak formaldehyde exposure category (
4 parts per million [ppm] vs >0 to <2.0 ppm) and all lymphohematopoietic malignancies (RR = 1.37; 95% CI = 1.03 to 1.81, P trend = .02) and Hodgkin lymphoma (RR = 3.96; 95% CI = 1.31 to 12.02, P trend = .01). Statistically nonsignificant associations were observed for multiple myeloma (RR = 2.04; 95% CI = 1.01 to 4.12, P trend > .50), all leukemia (RR = 1.42; 95% CI = 0.92 to 2.18, P trend = .12), and myeloid leukemia (RR = 1.78; 95% CI = 0.87 to 3.64, P trend = .13). There was little evidence of association for any lymphohematopoietic malignancy with average intensity or cumulative exposure at the end of follow-up in 2004. However, disease associations varied over time. For peak exposure, the highest formaldehyde-related risks for myeloid leukemia occurred before 1980, but trend tests attained statistical significance in 1990 only. After the mid-1990s, the formaldehyde-related risk of myeloid leukemia declined.
Conclusions: Evaluation of risks over time suggests a possible link between formaldehyde exposure and lymphohematopoietic malignancies, particularly myeloid leukemia but also perhaps Hodgkin lymphoma and multiple myeloma. Observed patterns could be due to chance but are also consistent with a causal association within the relatively short induction–incubation periods characteristic of leukemogenesis. Further epidemiological study and exploration of potential molecular mechanisms are warranted.
| CONTEXT AND CAVEATS Prior knowledge Previous analysis of data from a cohort of workers in formaldehyde industries and data from other epidemiologic studies suggested that exposure to this carcinogen was associated with increased risk of leukemia. Study design Prospective cohort study of workers who had been employed in formaldehyde industries. Exposure was estimated based on work histories, and deaths and causes of deaths were obtained from the National Death Index. Poisson regression was used to calculate risks of death from lymphohematopoietic malignancies associated with formaldehyde exposure. Contribution The long-term follow-up of industrial workers in this study suggested a possible association between formaldehyde exposure and mortality due to lymphohematopoetic malignancies, particularly myeloid leukemia. Implications Further epidemiological studies to evaluate risks of leukemia and lymphatic tumors in formaldehyde-exposed populations are warranted. Limitations This study relied on death certificate data, which may lack specificity with respect to sub-types of disease. From the Editors
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Manuscript received August 18, 2008; revised March 9, 2009; accepted March 18, 2009.
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