Genes That Modify Cancer Predisposition

27 May

In the earlier part of this chapter we discussed specific genes, abnormalities of which lead to the development of specific neoplasms, usually in a fairly high percentage of affected individuals. However, in multifactorial genetic traits, as noted above, a number of genes may be involved in the expression of a predisposition to neoplastic disease. This may be the case even in those situ- ations where cancer predisposition  may result from mutations in a tumor suppressor or proto- oncogene. Obvious proof of this latter statement is the fact that germline inherited mutations in tumor suppressor genes do not result in neoplasms of all tissues, proliferating or not, but usually only in certain tissues of the organism. Presumably, genes expressed in some tissues prevent the neoplastic transformation seen in other tissues. Furthermore, it is well known that exposures to carcinogenic agents will result in only a proportion of the exposed individuals developing can- cer. This may be due in part to a dose-response effect; but if the population is exposed to basi- cally the same dose throughout, then the differential neoplastic response is probably the result of individual differences in susceptibility during the development of neoplasia.

It has been estimated that up to 20% of all cancers in humans exhibit some form of inher- ited predisposition (Müller and Scott, 1994). In many of these examples, it is likely that the basic stimulus for the development of neoplasia is genetic and that environmental factors acting on a variety of genes may alter the expression and neoplastic potential of the one or two critical genes involved.  On the other hand, the major etiological  factors for cancer development  may be environmental, but the induction of neoplasia by environmental carcinogenic influences is mod- ified by the expression of various genes within the organism. It is not always easy to distinguish these two “pathways,”  and in a number of instances  one may make a cogent argument  that modifying  genes affect neoplastic  development  no matter what the inciting cause, genetic or environmental.

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