Re: "Mortality from Solid Cancers among Workers in Formaldehyde Industries"

Robert E. Tarone1,2 and Joseph K. McLaughlin1,2

1 International Epidemiology Institute, Rockville, MD 20850
2 Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232

Hauptmann et al. (1Go) concluded that their analyses of a cohort of industrial workers from 10 US formaldehyde-producing or -using facilities supported a possible causal association between formaldehyde exposure and nasopharyngeal cancer risk. They acknowledged that most nasopharyngeal cancers were observed in one of the 10 facilities included in their study (i.e., plant 1) and reported the results of analyses adjusted for facility, but the extent to which the increased rate of nasopharyngeal cancer among exposed workers in the US cohort was concentrated in plant 1 may not be clearly conveyed in their report. In table 1, we show results from the standardized mortality analysis of nasopharyngeal cancer in the US cohort by formaldehyde exposure status and facility (i.e., plant 1 vs. plants 2–10). We thank Dr. Michael Hauptmann for providing the expected values.


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TABLE 1. Results from the standardized mortality analysis of nasopharyngeal cancer in the US cohort of Hauptmann et al. (1Go), by formaldehyde exposure status and facility

 
The absence of evidence of increased risk in exposed workers from nine of the 10 facilities studied, as well as the magnitude of the difference between the standardized mortality ratio (SMR) for exposed workers from plant 1 and the SMR for exposed workers in the remaining nine plants (exact two-sided p value = 0.0012), raises serious questions about the interpretation of the risk estimates (adjusted or unadjusted for facility) from the US cohort as supporting a possible association between formaldehyde exposure and nasopharyngeal cancer risk.

Two other occupational cohort studies have examined the possible association between formaldehyde exposure and nasopharyngeal cancer risk. For a cohort of United Kingdom (UK) industrial workers exposed to formaldehyde, Coggon et al. (2Go) reported one nasopharyngeal cancer death as compared with 2.0 expected deaths. The UK cohort had over five times as many workers exposed to formaldehyde at time-weighted average levels exceeding 2 ppm as the US cohort (3Go, 4Go), but the only nasopharyngeal cancer death in the UK cohort was in a man whose formaldehyde exposure was classified as low (i.e., time-weighted average exposure of 0.1–0.5 ppm) (2Go). For a cohort of US garment workers, Pinkerton et al. (5Go) reported no nasopharyngeal cancer deaths versus 0.96 expected. Thus, in the combined experience of formaldehyde-exposed workers in plants 2–10 of the US industrial cohort, the UK industrial cohort, and the US garment worker cohort, there have been three observed nasopharyngeal cancer deaths as compared with 6.11 expected deaths (SMR = 0.5, 95 percent confidence interval: 0.1, 1.4). With the exception of workers from plant 1 of the US industrial cohort, there is little evidence to support an association between formaldehyde exposure and nasopharyngeal cancer risk.

In follow-up of a larger cohort of plant 1 workers, one additional nasopharyngeal cancer death in a formaldehyde-exposed worker was identified (6Go). In spite of the fact that three of the six nasopharyngeal cancer deaths reported by Hauptmann et al. (1Go) in plant 1 and the additional nasopharyngeal cancer death reported by Marsh et al. (6Go) in plant 1 occurred in workers who had been exposed to formaldehyde for less than 8 months, investigations of plant 1 have not yet documented any uniquely dangerous characteristics of formaldehyde exposure in the facility (6Go–11Go). Further intensive investigations of plant 1 are warranted before the elevated rates of nasopharyngeal cancer death in the US industrial cohort can be interpreted as supporting a possible causal association between formaldehyde exposure and nasopharyngeal cancer risk.

References

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  2. Coggon D, Harris EC, Poole J, et al. Extended follow-up of a cohort of British chemical workers exposed to formaldehyde. J Natl Cancer Inst 2003;95:1608–15.[Abstract/Free Full Text]
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