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A second point concerns the temporal relationship between the formaldehyde Monograph and IARC’s amended guidelines (the Preamble). The formaldehyde Working Group met and developed its conclusions in June 2004. The Preamble amendment process2 began in March 2005 and IARC posted the draft Preamble on its website for public comment from August to October 2005. Huff and Infante find fault that I wrote, “During 2005 IARC is updating the Preamble . . .”3 This statement appears in the proceedings of a September 2005 conference where I encouraged participants to examine the draft Preamble while the comment period was still open.
Third, Huff and Infante demand that “ALL exposure-associated tumour sites should be identified for ALL human carcinogens.” This is, in fact, done in the critical review portion of each Monograph, which discusses all tumour sites that have been studied and identifies all sites where increased risks were observed. The full list of sites is not obvious, however, because only the major findings appear in the short summary and evaluation sections and only these shorter sections have been available online. To increase public access to this information, IARC has begun making the full text of all Monographs freely available on its website (http://monographs.iarc.fr/). In the most recent formaldehyde Monograph,4 for example, the critical review identifies statistically significant associations for cancers of the lung, nasal cavity, nasopharynx, and hypopharynx; for lymphohaematopoietic cancer including myeloid leukaemia; for uveal melanoma and cancers of the brain and central nervous system, pancreas, salivary gland, rectum, and female breast; and for all cancers combined. After considering the epidemiological evidence overall, the Working Group highlighted in the short summary the strongest of these associations: nasopharyngeal cancer, leukaemia, and sinonasal cancer. Indeed, IARC is the first public agency to highlight the strong evidence associating formaldehyde with leukaemia.
A related question is whether to take a different approach and not to identify tumour sites at all in the final evaluation. The crux of the matter is whether to regard a list of tumour sites restrictively, as a finite number of sites where carcinogenesis is possible, or expansively, as examples where strong evidence exists at the time. IARC takes the expansive view and recognizes the likelihood that an agent may also cause cancer at other sites and by other mechanisms. For example, tobacco, first identified as a cause of lung cancer in smokers, has since been established to cause cancer at more than a dozen other sites and also in nonsmokers exposed to tobacco smoke.
Finally, Huff and Infante suggest that IARC should be re-evaluating probable and possible carcinogens during 2009 rather than continue its plan5 to review known human carcinogens (IARC Group 1) in Monograph Volume 100. A key objective of IARC’s plan for this volume, developed in collaboration with an international Advisory Group,6 is to elucidate mechanisms known to cause cancer in humans. IARC expects that future Monographs will use this information to identify additional carcinogens that act through similar mechanisms. In addition, epidemiologists can use mechanistic information to identify pre-cancerous biomarkers that can be measured long before tumours can be observed. We are convinced that taking this year to bring together information about mechanisms known to cause cancer will promote earlier identification of carcinogens in the future, including new chemicals and complex exposures that have not or cannot be studied by epidemiology. This is better than waiting decades for studies to document avoidable cancers in humans and would be a great achievement for workers and public health.
Head, IARC Monographs Programme
International Agency for Research on Cancer, Lyon, France
Competing interests: None declared
1. Huff J, Infante P. Identifying cancer sites for human carcinogens in the IARC monographs. Occup Environ Med 2009;66:140.
2. Preamble amendment process. http://monographs.iarc.fr/ENG/Preamble/amendments.php (accessed January 2009).
3. Cogliano VJ. Use of carcinogenicity bioassays in the IARC Monographs. Ann N Y Acad Sci 2006:1076:592–600.
4. Formaldehyde. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol 88, Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol. Lyon France: International Agency for Research on Cancer, 2006;39–325. http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php (accessed January 2009).
5. Future Meetings. http://monographs.iarc.fr/ENG/Meetings/index.php (accessed January 2009).
6. Report of the Advisory Group to Plan Volume 100: A Review of Human Carcinogens. Lyon France: International Agency for Research on Cancer, 2007, IARC Int Rpt 07/001. http://monographs.iarc.fr/ENG/Publications/internrep/07-001.pdf (accessed January 2009).
Editor’s Note: When we receive letters commenting on material published in OEM, it is our policy to allow the original authors an opportunity to see those letters in advance of publication and, if they wish, to respond to them in a letter published simultaneously. We failed to do this with the letter submitted by Drs. Huff and Infante. We apologize for this error. Dr. Cogliano’s response appears on this page.