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  • When the first edition of this book was published in 1960, chapters on cancer were neither numerous nor prominent. Although it was realized that some rare kindreds were prone to neoplasia, it was not known whether genes played a significant role in the common forms of cancer. Moreover, the biochemical and physiological bases of tumorigenesis were so poorly understood that it would have been impossible to write anything relating genes to cancer that was not speculative.

  • This has now changed dramatically, due to the revolution in cancer research that has occurred in the last two decades. If this revolution were to be summarized in a single sentence, that sentence would be “Cancer is, in essence, a genetic disease.” Although cancer is complex, and environmental and nongenetic factors clearly play a role at many stages of the neoplastic process, the tremendous progress made in understanding tumorigenesis is in large part due to the discovery of the genes that, when mutated, lead to cancer. The eighth edition of this book pays tribute to this revolution by including over 40 chapters describing the genetics and biochemical basis of cancers of various organs.

  • The genetics of cancer are clearly more complex than most of the other diseases described in this book. In this introductory chapter we attempt to answer some basic questions about this topic that hopefully will help put the chapters on cancer in perspective and explain their organization.


The simplest genetic diseases (e.g., Duchenne muscular dystrophy; see The Muscular Dystrophies) are caused by inherited mutations in a single gene that are necessary and sufficient to determine the phenotype (Fig. 26-1). This phenotype generally can be predicted from knowledge of the precise mutation, and modifying genes or environmental influences often play little role. More complex are certain diseases in which single defective genes can predispose patients to pathologic conditions, but the defective gene itself is not sufficient to guarantee the onset of clinically manifest disease. For example, patients who inherit defective low density lipoprotein receptor encoding genes are prone to atherosclerosis, but environmental influences, particularly dietary lipids, play a large role in determining the severity of disease (see Familial Hypercholesterolemia).

Fig. 26-1

Comparison of genetic diseases. Three types of genetic diseases, of increasing complexity, are illustrated (Reprinted by permission from Kinzler KW and Vogelstein B: Lessons from hereditary colon cancer Cell 87:161, 1996; copyright 1996 by Cell Press.)

Certain cancers display an obvious hereditary influence, but like atherosclerosis, the defective inherited gene is itself not sufficient for the development of cancer. Cancers only become manifest following accumulation of additional somatic mutations. These occur either as a result of the imperfection of the DNA copying apparatus (~10−10 mutations per base pair per somatic cell generation) or ...

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