Metabolic polymorphisms in carcinogen metabolising enzymes and cancer susceptibility.

Molecular genetic analysis is providing us with enormous advances in understanding the pathogenesis of human diseases such as cancer. The study of familial disease and the subsequent mapping and identification of the mutations which contribute to disease susceptibility, is not only providing insights into the factors involved in the pathogenesis of the disease but also identifying new targets for therapy. It is now clear that human tumours result from a complex sequence of mutation events. Each individual step makes the mutated cell more independent of its normal growth regulatory processes, eventually resulting in the formation of a metastatic tumour. There are a multitude of biochemical changes that these mutations confer, which provide preneoplastic cells with a selection advantage. In addition to an increased rate of cell division, such changes may make the cells resistant to cytotoxic insult or to programmed cell death. They can also confer an increased ability to survive independent of a normal hormonal environment. It is now clear that all these types of change may contribute to tumour cell progression.