The genetic influences as a factor in carcinogenesis
Radnofsky, Matthew Igor
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Evidence is presented to show that carcinogenesis is affected by heredity. However, of equal importance are internal factors such as hormonal, environmental and virus influences. The works of Strong (1935), Russell and Green (1943) and Andrevont (1948), among others, are used to show the inter-relationship of these factors. The entire theory was set down in formula form by Loeb in 1916, HS=C, where H stands for the heritable gene, S for the external environment, and C the resultant cancer. There are various theories as to how cancer occurs. Many of the statements can be reduced to the theory of somatic mutation, which causes the rapid and uncontrolled proliferation of the cells. However, the means whereby the cells become mutants has been attributed to various methods. Bittner's virus factor, Murphy's virus acting upon the chromatin and Needham's theory of the evocator action of the virus extract compared with the neural plate induction in embryology are all briefly discussed. The methods for obtaining accurate information on cancer inheritance are discussed at some length. The importance of inbreeding and of using the resultant pure bred strains is stressed by citing the classical argument between Slye and Little (1928), whose work on the same animals gave diametrically opposite results. In ordinary cases of inbreeding, it is usually possible to develop an animal strain that is either pure recessive or pure dominant. However, by using data compiled by Dr. Little and his associates (1943), it has been demonstrated that by examining highly inbred cancerous mice of known parentage, no pure dominants or recessives are found. To the contrary, none of the strains develops a one hundred per cent susceptibility to all types of tumors, nor are any one hundred per cent resistant. All the intermediate percentages are found. This seems to indicate that the method of transmission is one of multiple factors. Added proof of this method of transmission is suggested by the works of Andrevont and Heston whose work on the pulmonary tumors of mice seems to corroborate the multiple factor method. The difficulty involved in studying the heredity of cancer in human beings is explained by the small families involved, the reluctance of families to offer accurate information, the long period between generations and uncertainty of diagnoses. Man and the experimental animals used are both multicellular organisms. They probably both obey the Mendelian laws of inheritance. Therefore, the data obtained from animal experimentation can be reasonably applied to human beings. Wells (1930) described a mouse with a broken tooth which irritated the mucous membrane of the mouth. The resultant cancer spread to surrounding areas and caused ultimate pressure on the brain. Identical symptoms of cancer have been noted in human patients. Although it is likely that human beings obey Mendelian inheritance laws, no definite evidence has been presented that human carcinoma obeys these laws. This is not to suggest that the lair has been broken, but merely to show that the mode of transmission is probably one of multiple factors complicated by external factors such as the aforementioned hormonal and environmental influences. The relation of Mendelian laws of heredity to the incidence of cancer may be produced by a somatic mutation. The rate of occurence of this mutation is in turn influenced by genetic factors. Certain measures have been recommended for the future control of this disease which strikes one person in eight in the United States. Persons whose family tree shows a large percentage of cancer should avoid chronic irritations of any form. They should refrain from working in industry where they may be exposed to any of the carcinogens such as mineral oil, tar or coal tar products, paraffin or the other carcinogenic agents. Finally, as a general preventive measure, a person who has a family history of multiple carcinoma should not marry a person who has a similar history. Eugenic control of high cancer ratio families is in the long run a possible way of eradicating this disease.
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