Results from an ongoing study of workers employed at plants that used or produced formaldehyde continue to show a possible link between formaldehyde exposure and death from cancers of the blood and lymphatic system, particularly myeloid leukemia. The report, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, provides an additional 10 years of follow-up data to build on previous findings from this study. The report appeared online May 12, 2009, and in print May 20, 2009, in the Journal of the National Cancer Institute.

"The overall patterns of risk seen in this extended follow-up of industrial workers, while not definitive, are consistent with a causal association between formaldehyde exposure and cancers of the blood and lymphatic system and warrant continued concern. Further studies are needed to evaluate risks of these cancers in other formaldehyde-exposed populations and to assess possible biological mechanisms," said lead author of the report, Laura E. Beane Freeman, Ph.D., NCI Division of Cancer Epidemiology and Genetics.

Formaldehyde is widely used for industrial purposes and as a preservative and disinfectant. The International Agency for Research on Cancer classifies this chemical as a human carcinogen, based primarily on its association with nasopharyngeal cancer. In 1995, the U.S. Occupational Safety and Health Administration estimated that approximately 2.1 million workers in the United States were exposed to formaldehyde.

Since the 1980s, NCI has studied cancer deaths among a group of 25,619 workers, predominately white males, who were employed before 1966 in 10 industrial plants that produced formaldehyde and formaldehyde resin and that used the chemical to produce molded-plastic products, decorative laminates, photographic film, or plywood. In a previous report from this study, which included data on cancer deaths through 1994, researchers showed that the risk of death from leukemias (myeloid leukemia in particular) increased with higher levels of formaldehyde exposure.

In this report, which includes an average follow-up of over 40 years, researchers found a statistically significant association between death from all blood and lymphatic cancers combined and peak formaldehyde exposure. Workers with the highest peak exposures had a 37 percent increased risk of death compared to those with the lowest level of peak exposures. This represents an excess risk of death from several specific cancers, including Hodgkin's lymphoma, multiple myeloma, and myeloid leukemia -- the type most often associated with chemical exposure.

In this study, the risk of death from myeloid leukemia was 78 percent higher among industrial workers with the highest peak exposures compared to those with the lowest peak exposures. Excess risks of death from myeloid leukemia have also been reported among pathologists, embalmers, and other professionals who experience high-intensity peak exposures to formaldehyde. The highest level of increased risk of death from myeloid leukemia in this study occurred early on and has been declining steadily over time. This pattern could be due to chance, but the investigators note that similar patterns of risks over time have been seen for agents that are known to cause leukemia relatively soon after exposure.

"We know that various groups of professionals who may experience high peak exposures to formaldehyde are at increased risk of leukemia, but the evidence from studies of industrial workers, among whom exposure levels and patterns may be more variable, has been conflicting. The fact that we see an excess in this study of industrial workers, which is both the largest and the one with the most extensive exposure assessment, is notable," said Beane Freeman.

Based on the available data, scientists have not been able to identify a mechanism for how normal white blood cells might become leukemic following exposure to formaldehyde, because there is no direct evidence that formaldehyde damages cells in the bone marrow. However, studies of humans exposed to inhaled formaldehyde have shown higher rates of damage to their chromosomes in a type of mature white blood cells compared with rates in individuals who were not exposed to formaldehyde. Although the relevance to the development of leukemia of such chromosomal damage to mature white blood cells is not clear, agents that cause leukemia are also known to be associated with chromosomal aberrations in the peripheral blood cells of humans.

This study is also the first to report a statistically significant association between a chemical exposure and increased risk of death from Hodgkin lymphoma. Although based on a small number of deaths, the finding may warrant further study.

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For a fact sheet on cancer risk due to formaldehyde exposure, please go to http://www.cancer.gov/cancertopics/factsheet/Risk/formaldehyde.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

For more information on Dr. Beane Freeman's research, please go to http://dceg.cancer.gov/about/staff-bios/beane-freeman-laura.

Reference: Beane Freeman LE, Blair A, Lubin JH, Stewart PA, Hayes RB, Hoover RN, and Hauptmann M. Mortality from Lymphohematopoietic Malignancies Among Workers in Formaldehyde Industries: The National Cancer Institute Cohort. May 20, 2009, JNCI, Vol. 101, No. 10.

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