Causes
and Symptoms
Cancer
is generally thought to result from one or more permanent genetic changes
in a cell. In some cells a single mutational event can lead to neoplastic
transformation, but for most tumors it appears that carcinogenesis is
a multistep process. Although some rare congenital conditions lead to
cancer in infancy, the vast majority of human cancers arise as a result
of the complex interplay between genetic and environmental factors. Without
question, there are forms of cancer clearly related to particular environmental
exposures; it is equally clear, however, that these factors act on a genetic
substrate that may be either susceptible or resistant to the development
of cancer.
The emergence of cancer appears to involve the accumulation of genetic
damage in a target tissue. Such complex genetic changes specific to tissues
appear to underlie the progression to cancer. Such multistep progression
is quite complicated to study in experimental systems. Much work has focused
on the identification, isolation, and characterization of oncogenes, which
have the ability to transform normal cells into cancer cells. More than
50 bona fide or putative oncogenes have been characterized and mapped
throughout the human genome.
Environmental factors involved in the development of cancers can be chemical,
physical, or biological carcinogenic agents. At least three stages occur
in the natural history of cancer development from environmental factors.
The first stage is initiation, which is a specific alteration in the deoxyribonucleic
acid (DNA) of a target cell; environmental agents may act by inducing
expression of oncogenes. The second phase, promotion, involves the reversible
stimulation of expansion of the initiated cell or the reversible alteration
of gene expression in that cell or its progeny. Because promotion is thought
to be reversible, it is a target for prevention. The final phase of carcinogenesis
is progression. It is characterized by the development of aneuploidy and
clonal variation in the tumor; these in turn result in invasiveness and
metastasis.
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