Evolutionary aspects of human cancer.
Evolutionary aspects of human cancer can be dealt with at two levels--on the one hand long-term evolution involving hereditary effects between generations; and on the other hand evolutionary processes operating within the organisms between tissues, cells and cell constituents, which also comprise genetic alterations, selection and adaptation. These two levels of evolution can be designated as phylogenetic and ontogenetic evolution, respectively. Concerning phylogenetic evolution there must have been a strong selection against neoplastic diseases occurring at reproductive age and a variety of protective mechanisms against carcinogenic agents have been developed. Cancer is therefore primarily a disease of old age, which does not constitute a significant risk in natural populations for the simple reason that the life length is too short. The development of an individual comprises selection forces between cells and tissues, which are particularly striking for the multistage development of tumours. The accumulation of several genetic alterations in the same cells, as illustrated by the analysis of colorectal tumours, must require a pronounced clonal expansion between each event. Such selective growth effect has recently been demonstrated for the tumour suppressor gene p53 in brain tumours. Cancer often implies a break down of between balanced systems antagonistic forces, such as oncogenes and suppressors of oncogenes. Examples of this are provided by the genetic regulation of metastasis, involving metalloproteinase as well as the inhibitor of metalloproteinase. The immortalization of cells by transformation points to the fact that programmed cell death and the balance between suicide genes and suppressors of such suicide genes is affected.
Ramel
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Department of Genetic and Cellular Toxicology, Stockholm University, Sweden.
D017209:Apoptosis; D005075:Biological Evolution; D003043:Cocarcinogenesis; D006801:Humans; D008017:Life Expectancy; D008136:Longevity; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species