Environmental Factors
Summary of Key Points
History of Identification of Human Carcinogens
• The carcinogenic effects of many environmental and occupational agents were first described in humans.
• Beginning in the 20th century with the advent of animal bioassay programs, evidence of carcinogenicity in experimental animals has preceded evidence from epidemiological or case studies in humans.
• Most human cancers probably result from the interaction of several or more carcinogenic influences (often unidentified) along with intrinsic factors (e.g., inherited genes, hormones, and immune status).
Role of Environmental Agents in the Etiology of Human Cancer
• Although the causes of many human cancers remain unidentified, cumulative data support the opinion that environmental or dietary agents are the principal cause of human cancers.
• Cigarette smoking could be responsible for 25% of all cancers in the United States.
• Chemical carcinogens include aromatic amines, benzene, aflatoxins, tobacco chemicals, and chemotherapeutic agents.
• Radiation carcinogens include ultraviolet radiation, ionizing radiation, and radon.
• A number of metal carcinogens have been identified, including arsenic, nickel, cadmium, and chromates. These carcinogens have been associated largely with occupational exposures.
• Fibers (e.g., asbestos and silica) and dusts are well established as etiologic agents in lung cancers and mesothelioma.
• Many components in the diet can influence the development of cancer through carcinogenic or anticarcinogenic mechanisms.
Exposure Biomarkers, Susceptibility Factors, and Chemoprevention
• The identification of molecular biological markers of exposure, effect, and susceptibility (reflecting events before clinical disease) will help further our understanding of human carcinogenesis.
• The characterization of the human genome has permitted study of the roles of common polymorphisms in carcinogen metabolism or of DNA repair genes in susceptibility to cancer.
• Primary and secondary approaches to the prevention of cancer will be greatly facilitated by the development of noninvasive biomarkers that identify high-risk individuals.
• Tertiary prevention also might be enhanced by characterizing cancers with respect to etiology, genetic profile, or metabolic capacity.
1. Epidemiological results supporting the view that environmental factors are causally related to human cancer include:
A Large variations in specific cancer incidence are observed between countries or geographic regions.
B Migrant populations assume the cancer incidence profile of their new area within one or two generations.
C Cancer rates within a population can change rapidly—within decades.
2. The total number of chemicals, chemical mixtures, biological agents, physical agents, or industrial processes that have been classified as class 1 human carcinogens by the International Agency for Research on Cancer is about:
3. Which of the following agents is responsible for the most cancer mortality worldwide?
1. Answer: D. Rapid changes in risk for specific cancers indicate that extra-constitutional factors driven by the environment, lifestyle, and behavior have profound effects on the carcinogenic process. These factors in turn may be effectors of genetic and epigenetic changes in individuals. Overall, genetic change in populations occurs slowly.
2. Answer: A. It is estimated that more than 70,000 chemicals are currently in commercial use. Although only 100 or so have been determined to be human carcinogens, most of the remainder have not been rigorously tested. Nonetheless, it is likely that most important human carcinogens have been identified at this time.
3. Answer: B. Tobacco use causes more cancer deaths worldwide than any other human activity and is associated with cancers at many organ sites. Promotion of smoking in developing countries and promulgation of new tobacco products presage a global epidemic of tobacco-related diseases in coming decades.
