The Science and Practice of Carcinogen Identification and Evaluation
Cogliano, Vincent James, Baan, Robert A., Straif, Kurt, Grosse, Yann, Secretan, Marie Beatrice, El Ghissassi, Fatiha, Kleihues, Paul, Environmental Health Perspectives
Several national and international health agencies have established programs with the aim of identifying agents and exposures that cause cancer in humans. Carcinogen identification is an activity grounded in the scientific evaluation of the results of human epidemiologic studies, long-term bioassays in experimental animals, and other data relevant to an evaluation of carcinogenicity and its mechanisms. In this commentary, after a brief discussion of the science basis common to the evaluation of carcinogens across different programs, we discuss in more detail the principles and procedures currently used by the IARC Monographs program. Key words: carcinogen, carcinogen identification, conflict of interests, hazard identification, IARC Monographs.
The global burden of cancer continues to increase. There were an estimated 10.1 million new cases, 6.2 million deaths, and 22.4 million persons living with cancer in the year 2000 (Kleihues and Stewart 2003). This represents an increase of 19% in incidence and 18% in mortality since 1990. Given current trends in smoking prevalence and other factors, the annual number of new cases is estimated to reach 15 million by 2020. It is possible to prevent at least one-third of these new cases through better use of existing knowledge.
Understanding how cancer develops creates opportunities for cancer prevention or early detection. An important part of this effort is to identify the agents and exposures that cause cancer. Several national and international health agencies have established carcinogen identification programs that provide a scientific basis for governmental and private efforts to control cancer by reducing exposure to known and suspected human carcinogens.
The IARC Monographs on the Evaluation of Carcinogenic Risks to Humans are published by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO). Each IARC Monograph represents the consensus of an international working group of expert scientists. The IARC Monographs include a critical review of the pertinent peer-reviewed scientific literature as the basis for an evaluation of the weight of the evidence that an agent may be carcinogenic to humans. Published continuously since 1972, the scope of the IARC Monographs has expanded beyond chemicals to include complex mixtures, occupational exposures, lifestyle factors, physical and biologic agents, and other potentially carcinogenic exposures. After publication of IARC Monograph volume 87, expected in 2004 or 2005, nearly 900 agents, mixtures, and exposures will have been evaluated. Among these, 91 have been characterized as carcinogenic to humans, 67 as probably carcinogenic to humans, and 240 as possibly carcinogenic to humans.
The U.S. National Toxicology Program (NTP; Research Triangle Park, NC, USA) publishes the Report on Carcinogens, which identifies and discusses substances that may pose a carcinogenic hazard to human health and to which a significant number of persons residing in the United States are exposed. Mandated in 1978 by an act of the U.S. Congress, the Report on Carcinogens lists agents as either "known to be a human carcinogen" or "reasonably anticipated to be a human carcinogen." One nongovernmental and two federal scientific committees review the nominations for listing in or delisting from the Report on Carcinogens. The director of the National Toxicology Program reviews the three groups' recommendations and all public comments before the Secretary of Health and Human Services reviews and approves the Report on Carcinogens (NTP 2002).
The U.S. Environmental Protection Agency (EPA) assesses the health hazards of chemical contaminants present in the environment. These assessments cover cancer and adverse effects other than cancer. The hazard assessments are coupled with dose-response assessments that the U.S. EPA uses in its regulatory and information programs. …