Somatic alterations and metabolic polymorphisms.

Cancer is a multistep process in which multiple genetic alterations occur, causing a cumulative adverse effect on the control of cell differentiation, cell division and growth control. Somatic alterations acquired at the level of the cell become fixed in the developing cancer as chromosomal translocations, deletions, inversions, amplifications or point mutations. Since the ultimate unit of susceptibility to carcinogens is at the level of the cell, somatic gene alterations play an important role in carcinogenesis, as all neoplastic tumours exhibit somatic alterations. The incorporation of somatic alterations, such as oncogenes and tumour-suppressor genes, into epidemiological research provides an opportunity to clarify the role of exposure, other genetic changes and prognosis in cancer pathogenesis. The manner in which environmental factors act to initiate, accelerate or retard neoplastic progression Is currently being investigated using somatic gene mutational spectra to identify specific etiological carcinogens. Exploring the relationships between germline and somatic alterations may help to identify the timing of genetic events, important etiological exposures and gene-gene epistatic phenomena. Examining somatic alterations within the context of carcinogen-metabolizing enzymes may elucidate specific carcinogenic mechanisms. The use of somatic alterations to predict prognoses for patients with various malignancies may also help to enhance our ability to define subgroups of patients with different disease courses and treatment responses.