AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 57:486–487 (2014)
Letter to the Editor
Mortality from Solid Tumors in the Updated NCI Formaldehyde Cohort The results of the updated analyses of mortality in the NCI formaldehyde industry worker cohort [Beane Freeman et al., 2013] are reassuring with regard to serious adverse health effects of occupational formaldehyde exposure. Internal analyses of formaldehyde exposure levels resulted in highly significant inverse associations between formaldehyde exposure and mortality from all causes, all non-malignant circulatory diseases and all non-malignant respiratory diseases for all three exposure metrics examined (i.e., peak exposure, average intensity, and cumulative exposure). Analyses of peak exposure also showed inverse associations between formaldehyde exposure and mortality from all malignancies, all solid cancers, all respiratory cancers, and lung cancer. In the updated follow-up of the NCI cohort there was one additional death from nasopharyngeal cancer (NPC) in a worker exposed to formaldehyde compared to 1.2 expected additional NPC deaths. The NPC death occurred in a worker in the lowest formaldehyde exposure category for each of the three exposure metrics. In internal analyses of all workers, the trend tests indicated no significant association between formaldehyde exposure level and risk of NPC death for any of the three exposure metrics. The new NPC death was observed in plant 3 of the NCI study. As has been reported previously, in occupational cohort studies worldwide, only plant 1 of the NCI study shows evidence of increased NPC risk in formaldehyde-exposed workers [Marsh and Youk, 2005; Tarone and McLaughlin, 2005; Bosetti et al., 2008; McLaughlin and Tarone, 2013]. Including the additional NPC death in plant 3, the estimated (based on relative contributions to person-years reported by Beane Freeman et al. [2013]) SMR for NPC among formaldehyde-exposed workers in plants 2–10 of the NCI cohort is 0.7 (95% CI, 0.2–2.2) based on 3 NPC
deaths. Including occupational cohort studies from around the world, but excluding plant 1 of the NCI study, the estimated summary SMR for formaldehyde-exposed workers is 0.6 (95% CI, 0.2–1.5) based on 5 NPC deaths [Edling et al., 1987; Bertazzi et al., 1989; Andjelkovich et al., 1995; Coggon et al., 2003; Bosetti et al., 2008; Beane Freeman et al., 2013; Meyers et al., 2013]. Thus, there is no evidence from occupational cohort studies worldwide that formaldehyde exposure is associated with NPC, other than a significant excess of NPC deaths limited to workers in plant 1 of the NCI study. Beane Freeman et al. [2013] cite the NCI embalmer case–control study [Hauptmann et al., 2009] in their discussion of evidence regarding possible brain cancer risk among formaldehyde-exposed workers, but ignore the embalmer study in their discussion of possible NPC risk from occupational formaldehyde exposure. The OR for NPC among embalmers was 0.1 (95% CI, 0.01–1.2), even though embalmers were reported to have the highest peak exposure to formaldehyde of any known occupation [Hauptmann et al., 2009]. A scientifically sound summary of all of the epidemiologic evidence regarding occupational formaldehyde exposure and NPC risk would conclude that something in plant 1 of the NCI study or associated with the geographic area containing plant 1 may have led to increased risk of NPC [Marsh et al., 2007], but that occupational exposure to formaldehyde is unlikely to be a risk factor for NPC [McLaughlin and Tarone, 2013].
Joseph K. McLaughlin, PhD* Robert E. Tarone, PhD International Epidemiology Institute Rockville, Maryland
Disclosure Statement: The authors report no conflicts of interests. Correspondence to: Joseph K.McLaughlin,PhD,International Epidemiology Institute, 1455 Research Blvd., Suite 550,Rockville, MD 20850. E-mail: [email protected]
REFERENCES
Accepted 8 October 2013 DOI10.1002/ajim.22275. Published online 5 February 2014 in Wiley Online Library (wileyonlinelibrary.com).
Andjelkovich DA, Janszen DB, Brown MH, Richardson RB, Miller FJ. 1995. Mortality of iron foundry workers: IV. Analysis of a subcohort exposed to formaldehyde. J Occup Environ Med 37:826–837.
ß 2014 Wiley Periodicals, Inc.
Letter to the Editor
Beane Freeman LE, Blair A, Lubin JH, Stewart PA, Hayes RB, Hoover RN, Hauptmann M. 2013. Mortality from solid tumors among workers in formaldehyde industries: An update of the NCI Cohort. Am J Ind Med 56:1015–1026. Bertazzi PA, Pesatori A, Guercilena S, Consonni D, Zocchetti C. 1989. Carcinogenic risk for resin producers exposed to formaldehyde: Extension of follow-up. Med Lav 80:111–122.
487
Mortality from lymphohematopoietic malignancies and brain cancer among embalmers exposed to formaldehyde. J Natl Cancer Inst 101:1696–1708. Marsh GM, Youk AO. 2005. Reevaluation of mortality risks from nasopharyngeal cancer in the formaldehyde cohort study of the National Cancer Institute. Regul Toxicol Pharmacol 42:275–283.
Bosetti C, McLaughlin JK, Tarone RE, Pira E, La Vecchia C. 2008. Formaldehyde and cancer risk: A quantitative review of cohort studies through 2006. Ann Oncol 19:29–43.
Marsh GM, Youk AO, Buchanich JM, Erdal S, Esmen NA. 2007. Work in metal industry and nasopharyngeal cancer mortality among formaldehyde-exposed workers. Regul Toxicol Pharmacol 48:308– 319.
Coggon D, Harris EC, Poole J, Palmer KT. 2003. Extended follow-up of a cohort of British chemical workers exposed to formaldehyde. J Natl Cancer Inst 95:1608–1615.
McLaughlin JK, Tarone RE. 2013. False positives in cancer epidemiology. Cancer Epidemiol Biomarkers Prev 22:11–15.
Edling C, Järvholm B, Andersson L, Axelson O. 1987. Mortality and cancer incidence among workers in an abrasive manufacturing industry. Br J Ind Med 44:57–59. Hauptmann M, Stewart PA, Lubin JH, Beane Freeman LE, Hornung RW, Herrick RF, Hoover RN, Fraumeni JF Jr, Blair A, Hayes RB. 2009.
Meyers AR, Pinkerton LE, Hein MJ. 2013. Cohort mortality study of garment industry workers exposed to formaldehyde: Update and internal comparisons. Am J Ind Med 56:1027–1039. Tarone RE, McLaughlin JK. 2005. Re:“Mortality from solid cancers among workers in formaldehyde industries.” Am J Epidemiol 161: 1089–1091.
Letter to the Editor
Mortality from Solid Tumors in the Updated NCI Formaldehyde Cohort The results of the updated analyses of mortality in the NCI formaldehyde industry worker cohort [Beane Freeman et al., 2013] are reassuring with regard to serious adverse health effects of occupational formaldehyde exposure. Internal analyses of formaldehyde exposure levels resulted in highly significant inverse associations between formaldehyde exposure and mortality from all causes, all non-malignant circulatory diseases and all non-malignant respiratory diseases for all three exposure metrics examined (i.e., peak exposure, average intensity, and cumulative exposure). Analyses of peak exposure also showed inverse associations between formaldehyde exposure and mortality from all malignancies, all solid cancers, all respiratory cancers, and lung cancer. In the updated follow-up of the NCI cohort there was one additional death from nasopharyngeal cancer (NPC) in a worker exposed to formaldehyde compared to 1.2 expected additional NPC deaths. The NPC death occurred in a worker in the lowest formaldehyde exposure category for each of the three exposure metrics. In internal analyses of all workers, the trend tests indicated no significant association between formaldehyde exposure level and risk of NPC death for any of the three exposure metrics. The new NPC death was observed in plant 3 of the NCI study. As has been reported previously, in occupational cohort studies worldwide, only plant 1 of the NCI study shows evidence of increased NPC risk in formaldehyde-exposed workers [Marsh and Youk, 2005; Tarone and McLaughlin, 2005; Bosetti et al., 2008; McLaughlin and Tarone, 2013]. Including the additional NPC death in plant 3, the estimated (based on relative contributions to person-years reported by Beane Freeman et al. [2013]) SMR for NPC among formaldehyde-exposed workers in plants 2–10 of the NCI cohort is 0.7 (95% CI, 0.2–2.2) based on 3 NPC
deaths. Including occupational cohort studies from around the world, but excluding plant 1 of the NCI study, the estimated summary SMR for formaldehyde-exposed workers is 0.6 (95% CI, 0.2–1.5) based on 5 NPC deaths [Edling et al., 1987; Bertazzi et al., 1989; Andjelkovich et al., 1995; Coggon et al., 2003; Bosetti et al., 2008; Beane Freeman et al., 2013; Meyers et al., 2013]. Thus, there is no evidence from occupational cohort studies worldwide that formaldehyde exposure is associated with NPC, other than a significant excess of NPC deaths limited to workers in plant 1 of the NCI study. Beane Freeman et al. [2013] cite the NCI embalmer case–control study [Hauptmann et al., 2009] in their discussion of evidence regarding possible brain cancer risk among formaldehyde-exposed workers, but ignore the embalmer study in their discussion of possible NPC risk from occupational formaldehyde exposure. The OR for NPC among embalmers was 0.1 (95% CI, 0.01–1.2), even though embalmers were reported to have the highest peak exposure to formaldehyde of any known occupation [Hauptmann et al., 2009]. A scientifically sound summary of all of the epidemiologic evidence regarding occupational formaldehyde exposure and NPC risk would conclude that something in plant 1 of the NCI study or associated with the geographic area containing plant 1 may have led to increased risk of NPC [Marsh et al., 2007], but that occupational exposure to formaldehyde is unlikely to be a risk factor for NPC [McLaughlin and Tarone, 2013].
Joseph K. McLaughlin, PhD* Robert E. Tarone, PhD International Epidemiology Institute Rockville, Maryland
Disclosure Statement: The authors report no conflicts of interests. Correspondence to: Joseph K.McLaughlin,PhD,International Epidemiology Institute, 1455 Research Blvd., Suite 550,Rockville, MD 20850. E-mail: [email protected]
REFERENCES
Accepted 8 October 2013 DOI10.1002/ajim.22275. Published online 5 February 2014 in Wiley Online Library (wileyonlinelibrary.com).
Andjelkovich DA, Janszen DB, Brown MH, Richardson RB, Miller FJ. 1995. Mortality of iron foundry workers: IV. Analysis of a subcohort exposed to formaldehyde. J Occup Environ Med 37:826–837.
ß 2014 Wiley Periodicals, Inc.
Letter to the Editor
Beane Freeman LE, Blair A, Lubin JH, Stewart PA, Hayes RB, Hoover RN, Hauptmann M. 2013. Mortality from solid tumors among workers in formaldehyde industries: An update of the NCI Cohort. Am J Ind Med 56:1015–1026. Bertazzi PA, Pesatori A, Guercilena S, Consonni D, Zocchetti C. 1989. Carcinogenic risk for resin producers exposed to formaldehyde: Extension of follow-up. Med Lav 80:111–122.
487
Mortality from lymphohematopoietic malignancies and brain cancer among embalmers exposed to formaldehyde. J Natl Cancer Inst 101:1696–1708. Marsh GM, Youk AO. 2005. Reevaluation of mortality risks from nasopharyngeal cancer in the formaldehyde cohort study of the National Cancer Institute. Regul Toxicol Pharmacol 42:275–283.
Bosetti C, McLaughlin JK, Tarone RE, Pira E, La Vecchia C. 2008. Formaldehyde and cancer risk: A quantitative review of cohort studies through 2006. Ann Oncol 19:29–43.
Marsh GM, Youk AO, Buchanich JM, Erdal S, Esmen NA. 2007. Work in metal industry and nasopharyngeal cancer mortality among formaldehyde-exposed workers. Regul Toxicol Pharmacol 48:308– 319.
Coggon D, Harris EC, Poole J, Palmer KT. 2003. Extended follow-up of a cohort of British chemical workers exposed to formaldehyde. J Natl Cancer Inst 95:1608–1615.
McLaughlin JK, Tarone RE. 2013. False positives in cancer epidemiology. Cancer Epidemiol Biomarkers Prev 22:11–15.
Edling C, Järvholm B, Andersson L, Axelson O. 1987. Mortality and cancer incidence among workers in an abrasive manufacturing industry. Br J Ind Med 44:57–59. Hauptmann M, Stewart PA, Lubin JH, Beane Freeman LE, Hornung RW, Herrick RF, Hoover RN, Fraumeni JF Jr, Blair A, Hayes RB. 2009.
Meyers AR, Pinkerton LE, Hein MJ. 2013. Cohort mortality study of garment industry workers exposed to formaldehyde: Update and internal comparisons. Am J Ind Med 56:1027–1039. Tarone RE, McLaughlin JK. 2005. Re:“Mortality from solid cancers among workers in formaldehyde industries.” Am J Epidemiol 161: 1089–1091.
