Genetic polymorphism and cancer susceptibility: fourteenth Sapporo Cancer Seminar.

It has long been recognized since the early studies in Japan by Yamagiwa and Ichikawa with coal tar-induced carcinogenesis that exposure to environmental and dietary chemicals are likely to be responsible for the vast majority of human cancers. A large number of enzymes participate in both activation and inactivation pathways of carcinogen metabolism. These enzymes mainly function in xenobiotic metabolism and are not thought to play critical roles in metabolism of endogenous chemicals such as hormones. A high degree of interindi vidual variability exists in levels of expression of xenobiotic-metabolizing enzymes, and some of this variability is due to genetic poly morphism. The critical roles of these enzymes in carcinogen metabolism and this genetic variability in their expression lead to the possibility that xenobiotic enzyme polymorphisms are associated with cancer risk. This risk would be manifest with environmental or dietary exposure to carcinogens. A number of genetic polymorphisms in P450s2 and transferase enzymes have been described, along with