The Genetic Basis of Human Cancer

No discipline has been impacted more by the recent advances in genetics and molecular biology than the fields of oncology and cancer research. In this exciting new title, renowned researchers and practitioners of current cancer and genetics research present a thorough review of the fundamentals of genetics and human phenotypes, gene mutation, the Human Genome Project, and genetic implanting. From relatively rare to massively prevalent oncologic diseases, the authors cover topics from melanoma, breast cancer to Wilms Tumor. Chapter organization reflects clinical aspects; genetic loci; specific genes; and implications for diagnosis.

During the past two decades, our knowledge of the pathogenesis of cancer has progressed from the unidimensional notion of cancer-causing, dominant mutations that accelerate growth (oncogenes) to a complex picture involving growth inhibition (tumor suppressors, or gatekeepers), programmed cell death (apoptosis genes), and more recently, elements that control the stability of DNA and chromosomes (caretakers). With each of these discoveries has come the opportunity for improved diagnosis and prognosis. Furthermore, the first generation of therapeutic products based on these insights is now entering clinical trials. Our understanding is at such a level of sophistication that for patients with a genetic predisposition to cancer, we can begin to contemplate intervention at the level of prevention and even gene therapy.

A task almost as challenging as elucidating mechanisms of carcinogenesis is producing a clear and comprehensive presentation of this new knowledge for readers with widely differing professional backgrounds and needs. The Genetic Basis of Human Cancer, which began as a mere chapter in another textbook, Metabolic and Molecular Bases of Inherited Disease (Seventh edition. Edited by Charles R. Scriver. New York: McGraw-Hill, 1995), is one of the most recent attempts to solve this pedagogic dilemma. The result is, with a few qualifications, quite successful.

There are two principal components of success in attempts to serve different readerships. The first is the recruitment of scientists and clinicians who have made important contributions to the field to write the chapters. The second involves the organization of the book. For nonexperts, the opening section of the book covers the fundamentals of human and cancer genetics and the second section summarizes recent advances in the study of growth control. For both cognoscenti and prepared novices, the book continues with a third, detailed section on specific familial cancer syndromes, partitioned according to the editors' "caretaker-gatekeeper" concept (a chapter on each syndrome, with particularly extensive offerings on breast and colon cancer), and a final section on 11 tumors that have no definitively identified genetic contributions and therefore are still being investigated.

The introductory section is quite ambitious, and some of its chapters, especially "The Nature of Human Gene Mutation," will be useful to expert and novice alike. The opening chapter, "A Human Genetics Primer," covers the ground from A, C, G, T, and the Watson-Crick model of DNA to the construction and use of transgenic animals as models of human disease. In between, the authors discuss, among other things, the genetic code, mendelian inheritance, linkage, imprinting, unstable mutations, recombinant DNA and polymerase-chain-reaction technology, methods for discovering mutations, and gene-environment interactions.

The book suffers greatly from a lack of color illustration, and some topics need more coverage. For example, the technology of human genetics -- gene arrays and DNA chips -- is advancing at a remarkable pace and is of intrinsic interest to experts and curious amateurs. There is no discussion of these and other advances, probably because of the usual lag between the writing and publication of textbooks. Also, the field of human-cancer genetics, like other areas of the field of genetic diseases, is moving from a view of hereditary cancers as a group of rare, highly penetrant, monogenic disorders such as neurofibromatosis to the working hypothesis that many cases represent the outcome of polygenic interactions. Thus, a more extensive treatment of genetic epidemiology seems warranted.

Finally, it is interesting to speculate about the future of such textbooks. In genetics, the Internet makes it possible to update students, clinicians, and scientists continually with new information. More important, this technology promotes the integration of new information with the old, thus advancing both learning and research. Will this be the last generation of stand-alone, printed reference books? Some combination of paper and electronics, in which the reader is able to have a hard copy of the basics but have access to updated and integrated information, seems like a good idea. Stay tuned to your favorite bookstore.

Reviewed by Theodore G. Krontiris, M.D., Ph.D.
Copyright © 1998 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.