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Armitage–Doll Multistage Model Of Carcinogenesis
The Armitage–Doll model is a statistical model of carcinogenesis, proposed in 1954 by Peter Armitage and Richard Doll, in which a series of discrete mutations result in cancer.Armitage, P. and Doll, R. (1954"The Age Distribution of Cancer and a Multi-Stage Theory Of Carcinogenesis" ''British Journ. of Cancer'', 8 (1), 1-12. Reprinted (2004)reprint ''British Journal of Cancer'', 91, 1983–1989. The original paper has recently been reprinted with a set of commentary articles. The model The rate of incidence and mortality from a wide variety of common cancers follows a power law: someone's risk of developing a cancer increases with a power of their age. The model is very simple, and reads \mathrm = \frac t^ in Ashley's notation.Ashley, D. J. B., Brit. J. Cancer, 23, 313 (1969) Their interpretation was that a series of r mutations were required to initiate a tumour. This is now widely accepted, and part of the mainstream view of carcinogenesis. In their original paper, they ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peter Armitage (statistician)
Peter Armitage CBE (born 15 June 1924) is a statistician specialising in medical statistics. Peter Armitage attended Huddersfield College and went on to read mathematics at Trinity College, Cambridge. Armitage belonged to the generation of mathematicians who came to maturity in the Second World War. He joined the weapons procurement agency, the Ministry of Supply where he worked on statistical problems with George Barnard. After the war he resumed his studies and then worked as a statistician for the Medical Research Council from 1947 to 1961. From 1961 to 1976, he was Professor of Medical Statistics at the London School of Hygiene and Tropical Medicine where he succeeded Austin Bradford Hill. His main work there was on sequential analysis. He moved to Oxford as Professor of Biomathematics and became Professor of Applied Statistics and head of the new Department of Statistics, retiring in 1990. He was president of the Royal Statistical Society in 1982–4. He was president of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Richard Doll
Sir William Richard Shaboe Doll (28 October 1912 – 24 July 2005) was a British physician who became an epidemiologist in the mid-20th century and made important contributions to that discipline. He was a pioneer in research linking smoking to health problems. With Ernst Wynder, Bradford Hill and Evarts Graham, he was credited with being the first to prove that smoking increased the risk of :lung cancer and :heart disease. (German studies had suggested a link as early as the 1920s but were forgotten or ignored until the 1990s.) He also carried out pioneering work on the relationship between radiation and leukaemia as well as that between asbestos and lung cancer, and alcohol and breast cancer. On 28 June 2012, he was the subject of an episode of ''The New Elizabethans'', a series broadcast on BBC Radio Four to mark the Diamond Jubilee of Queen Elizabeth II, dealing with 60 public figures from her reign. Biography Doll was born at Hampton, Middlesex (now part of south-we ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication (translesion synthesis). Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce detectable changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity. Mutation is the ultimate source o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Power Law
In statistics, a power law is a Function (mathematics), functional relationship between two quantities, where a Relative change and difference, relative change in one quantity results in a proportional relative change in the other quantity, independent of the initial size of those quantities: one quantity varies as a Exponentiation, power of another. For instance, considering the area of a square in terms of the length of its side, if the length is doubled, the area is multiplied by a factor of four. Empirical examples The distributions of a wide variety of physical, biological, and man-made phenomena approximately follow a power law over a wide range of magnitudes: these include the sizes of craters on the moon and of solar flares, the foraging pattern of various species, the sizes of activity patterns of neuronal populations, the frequencies of words in most languages, frequencies of family names, the species richness in clades of organisms, the sizes of power outages, volcanic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Retinoblastoma
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively found in young children. Though most children survive this cancer, they may lose their vision in the affected eye(s) or need to have the eye removed. Almost half of children with retinoblastoma have a hereditary genetic defect associated with retinoblastoma. In other cases, it is caused by a congenital mutation in the chromosome 13 gene 13q14 (retinoblastoma protein). Signs and symptoms Retinoblastoma is universally known as the most intrusive intraocular cancer among children. The chance of survival and preservation of the eye depends fully on the severity. Retinoblastoma is extremely rare as there are only about 200 to 300 cases every year in the United States. Looking at retinoblastoma globally, only 1 in about 15,000 children have ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Two-hit Hypothesis
The Knudson hypothesis, also known as the two-hit hypothesis, is the hypothesis that most tumor suppressor genes require both alleles to be inactivated, either through mutations or through epigenetic silencing, to cause a phenotypic change. It was first formulated by Alfred G. Knudson in 1971 and led indirectly to the identification of tumor suppressor genes. Knudson won the 1998 Albert Lasker Clinical Medical Research Award for this work. Knudson performed a statistical analysis on cases of retinoblastoma, a tumor of the retina that occurs both as an inherited disease and sporadically. He noted that inherited retinoblastoma occurs at a younger age than the sporadic disease. In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition. Knudson suggested that two "hits" to DNA were necessary to cause the cancer. In the children with inherited retinoblastoma, the first mutation in what later came to be identi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumour Suppressor Genes
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes. TSGs can be grouped into the following categories: caretaker genes, gatekeeper genes, and more recently landscaper genes. Caretaker genes ensure stability of the genome via DNA repair and subsequently when mutated allow mutations to accumulate. Meanwhile, gatekeeper genes directly regulate cell growth by either inhibiting cell cycle progression or inducing apoptosis. Lastly landscaper genes regulate growth by contributing to the surrounding environment, when mutated can cause an enviro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
