ABSTRACT
Cancer remains a leading cause of morbidity and mortality in the human population, and the costs to society of this dreaded disease are prodigious. Cancer is a group of diseases in which there is an uncontrolled proliferation of cells that express varying degrees of Þdelity to their precursor cell of origin. It has been proposed that cancer has six hallmarks: (1) self-sufÞciency in growth signals, (2) insensitivity to antigrowth signals, (3) evasion of apoptosis, (4) tissue invasion and metastasis, (5) sustained angiogenesis, and (6) limitless replicative potential. The induction of a neoplasm is a multistage process that occurs over a long period of time, decades in humans. These stages have been experimentally deÞned as initiation, promotion, and progression. The causes of most human cancers remain unidentiÞed; however, considerable evidence suggests that environmental and lifestyle factors, especially chemical agents, are important contributors. For example, tobacco smoking appears to be responsible for approximately 30% of all cancer deaths in developed countries. The notion that environmental agents are the principal causes of human cancers is largely derived from a series of epidemiological observations:
1. Although overall cancer incidence is reasonably constant between countries, incidences of speciÞc tumor types can vary up to several hundred-fold.
