Risk factors for cancer

Abstract

It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer. The most important carcinogenic chemicals are associated with life-style factors, whereas agents related to other environmental, occupational, or medical exposure are numerically less important. Most chemical agents exert their carcinogenic effects as electrophilic reactants covalently binding to DNA. Certain agents such as asbestos are carcinogenic by virtue of their physical properties. Several short-term tests have been used to screen for chemical carcinogens. Whole-animal studies remain the standard for predicting carcinogen risk in humans, although major limitations in such studies exist. Ionizing radiation also exerts its carcinogenic effect through damage to cellular macromolecules including DNA. Excess cancer risk appears after a latent period of several years following exposure. Risk increases in approximately a linear fashion in proportion to the radiation energy, cumulative dose, and a variety of host biologic factors. The greatest source of average radiation exposure to the US population is from the uranium decay product radon.(ABSTRACT TRUNCATED AT 400 WORDS)