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Early mathematical modeling of cancer, by Armitage and Doll, set the stage for the future development of the somatic evolutionary theory of cancer. Armitage and Doll explained the cancer incidence data, as a function of age, as a process of the sequential accumulation of somatic mutations (or other rate limiting steps). [13]
The somatic mutations and epigenetic alterations caused by DNA damage and deficiencies in DNA repair accumulate in field defects. Field defects are normal-appearing tissues with multiple alterations (discussed in the section below), and are common precursors to development of the disordered and over-proliferating clone of tissue in a cancer.
A somatic mutation is a change in the DNA ... Most mutagens act by causing DNA damage ... the role of somatic mutations in the development of cancer is well ...
DNA damage in non-replicating cells, if not repaired and accumulated can lead to aging. DNA damage in replicating cells, if not repaired can lead to either apoptosis or to cancer. The schematic diagram indicates the roles of insufficient DNA repair in aging and cancer, and the role of apoptosis in cancer prevention.
The likely major underlying cause of mutations in cancer is DNA damage. [citation needed] For example, in the case of lung cancer, DNA damage is caused by agents in exogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene). [25]
Mutation and DNA damage are the two major types of errors that occur in DNA, but they are fundamentally different. DNA damage is a physical alteration in the DNA structure, such as a single or double strand break, a modified guanosine residue in DNA such as 8-hydroxydeoxyguanosine, or a polycyclic aromatic hydrocarbon adduct. DNA damages can be ...
Such silencing likely acts similarly to a germ-line mutation in a DNA repair gene, and predisposes the cell and its descendants to progression to cancer. [35] Another review [36] points out that when a gene necessary for DNA repair is epigenetically silenced, DNA repair would tend to be deficient and DNA damages can accumulate. Increased DNA ...
Somatic enrichment for transversion mutations (G:C>T:A) has been associated with base excision repair (BER) deficiency and linked to defective MUTYH, a DNA glycosylase, in colorectal cancer. [17] Direct DNA oxidation damage leads to the creation of 8-Oxoguanine, which if remains un-repaired, will lead to incorporation of adenine instead of ...