Download e-book for kindle: Advances in Human Genetics 8 by Alfred G. Knudson Jr. (auth.), Harry Harris, Kurt Hirschhorn

By Alfred G. Knudson Jr. (auth.), Harry Harris, Kurt Hirschhorn (eds.)

ISBN-10: 1461582679

ISBN-13: 9781461582670

ISBN-10: 1461582695

ISBN-13: 9781461582694

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181 While the colon and endometrium have been the predominantly affected sites, others have been observed in excess. The tumors do seem to be adenocarcinomas, and Anderson3 has referred to the condition as hereditary adenocarcinomatosis. Since there are no noncancerous stigmata of this disorder, it is more difficult to follow the course of tumor development in a gene carrier. Nevertheless, the ages at first diagnosis of colon cancer can be used to construct age-specific prevalence curves. Such a procedure shows the curve to be later than that for polyposis, but still much earlier than that for colon cancer generally.

Since a mean of three or four tumors develop in each hereditary case, the dominant gene for retinoblastoma increases the risk of tumor from 3 per 100,000 to 3-4, or 100,000-fold. l58 The occurrence of the two forms is consistent with a two-mutation model that assumes that the second mutation must occur before differentiation and cessation of mitosis occur. Neuroblastoma has been noted above to have occurred a few times in patients with neurofibromatosis, but it is not otherwise associated with any predisposing genetic state, either chromosomal or genic.

Knudson, Jr. demonstrate DNA synthesis. 59 But the flat mucosal cells not involved in polyps show both patterns in familial polyposis; failure of repression of DNA synthesis is found with high frequency in mucosal patches. 60 It seems that the inherited mutation itself does not cause this aberrant DN A synthesis, but rather that such cells often lose the ability, spread by cell division into surface patches of similarly affected cells, and then grow into polyps. Some further change evidently precedes the development of carcinoma.

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Advances in Human Genetics 8 by Alfred G. Knudson Jr. (auth.), Harry Harris, Kurt Hirschhorn (eds.)


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