The majority of recognized carcinogens cause genetic mutations. Changes in gene expression in somatic cells, mostly due to mutation, are thought to be the basis for malignant transformation; there may be one or more, rare, dominantly inherited susceptibilities to every type of cancer. The contribution made by these highly penetrant, dominant susceptibilities to the total incidence of cancer has been estimated at 2-5% of fatal cancers. Genetic variation in susceptibility to cancer may also arise because of genetic polymorphism affecting the absorption, transport, metabolic activation, or detoxification of environmental carcinogens. A number of studies have suggested an interaction between some genetic polymorphisms and environmental carcinogens.
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