Solutions to Peto's Paradoxes and to Wright's Enigma have Implications for Cancer Prevention
Year: 2017
Type: article
Abstract: The power function is consistent with the concept of multiple hits leading to cancer and it was postulated that the hits were equivalent to deleterious mutations.Thus the simplest model is that the accumulation of n specific mutations in a single stem cell leads to cancer.But more complex models were soon proposed.One possibility is that cancer develops in stages, with initial mutations leading to clonal expansion and then subsequent mutations leading to cancer.In this case the number of mutations for malignancy (m) might be less than n.A second possibility is that the genome becomes progressively more unstable as mutations accumulate and in this case the value of m could be greater than n.Laboratory based experimental work in the 1980s and 1990s confirmed the prescient predictions of the above theoretical models [7][8][9][10].Oncogenes, which switch on growth, are kept in check by anti-oncogenes and by other tumour suppressive mechanisms.Thus it requires at least two deleterious mutations in one cell before uncontrolled growth occurs.Retinoblastoma is due to two mutations disabling both retinoblastoma genes and leading to the loss of the retinoblastoma gene transcription protein.But there are far more stem cells, and stem cell mitoses, in the colon, for instance, than in the retina, and colon cancer would be far more common than observed if only two deleterious 001
Author: Naseema Maria Begum
Institution: Royal Lancaster Infirmary
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W2736407231