Walter E. Heston, Ph.D. 



GENETICS <?/ NEOPLASIA 



The ultimate aim in the study of the genetics of neoplasia in laboratory mammals 

 is the control of cancer in man. In addition, however, such studies contribute much 

 to our general basic knowledge of physiologic genetics. The study of no character, 

 for example, has contributed more information on genes and their relationship to a 

 multitude of nongenetic factors in their paths of action than has the study of mammary 

 tumors in the mouse. It has been demonstrated that the etiology of this neoplasm 

 can include not only the inherited genetic factors but also a virus, exogenous and 

 endogenous hormonal factors, many physical and chemical carcinogens, nutrition, and 

 even temperature, all of which are interrelated in a unified picture of physiologic 

 genetics. It is likely that the etiologic picture of many of the other types of neoplasms 

 will eventually be shown to be equally complex and that all will include genie action. 



Anyone interested in undertaking a study of the genetics of neoplasia might well 

 start with a review and digest of Dr. Sewall Wright's papers on otocephaly and Poly- 

 dactyly in the guinea pig published nearly 30 years ago. 1414, 1433, 1451 In these studies 

 he established the basic concepts of the inheritance of multiple-factor characters with 

 alternative expression. He established that both genetic and nongenetic factors form 

 a continuous underlying variation, but because of certain thresholds the phenotypic 

 expression becomes discontinuous. The character appears when the combined action 

 of the genetic and nongenetic factors surpasses the threshold. Hence, Gruneberg 501 

 has more recently referred to this variation as being quasicontinuous, and Falconer 335 

 has called such characters threshold characters. At least most neoplasms, like oto- 

 cephaly and Polydactyly, are inherited as multiple-factor characters with alternative 

 expression, and this early work of Wright provides a firm basis for understanding their 



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