© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 1, 74-75,
January 5, 2000
© 2000 Oxford University Press
BOOK REVIEW |
Inherited Susceptibility to Cancer: Clinical, Predictive and Ethical Perspectives
William D. Foulkes, Shirley V. Hodgson, eds. Cambridge (U.K.): Cambridge University Press, 1998. 456 pp., illus. $95.00. ISBN 0-521-56340-2
Correspondence to: Randall Burt, M.D., University of Utah School of Medicine, GI Division, 50 N. Medical Dr., Salt Lake City, UT 84132.
Cancer has historically been considered a disease of environmental exposure with the exception of a few well-described, but rare, inherited syndromes. In the past 2 decades, it has become increasingly apparent that inherited susceptibility plays a much larger role in human cancer. Numerous cancer susceptibility genes have been identified, some of which relate to the known inherited syndromes and some of which do not. Genes that confer susceptibility to colon, breast, uterine, renal, and other malignancies are now known. Somatic inactivation of the genes related to inherited cancer syndromes has been found in many cases to be important to the molecular pathogenesis of sporadic forms of the corresponding malignancies. Equally important, knowledge of specific cancer susceptibility genes has led to the development of clinical genetic testing for cancer predisposition. The application of such testing, however, has raised many ethical, social, and legal questions and, in many cases, has changed the approaches to disease screening and management. All of these issues have been thrust on the clinician with frighteningly little guidance.
Inherited Susceptibility to Cancer, edited by William D. Foulkes and Shirley V. Hodgson, is a volume written to update and educate both the clinician and the genetic scientist with regard to the social and medical issues relevant to inherited cancer susceptibility. The book is divided into two interrelated parts. Social and ethical issues are reviewed in part I, along with cancer screening, genetic counseling, and pertinent genetic laboratory methods. Current knowledge is reviewed by organ in part II. The book finishes with chapters on inherited abnormalities of DNA processing, childhood cancer, and a helpful review of very recent developments.
Chapter 1 begins with a summary of the inherited basis of cancer. It presents a fascinating historical perspective of how heredity was finally recognized as relevant to cancer pathogenesis after substantial opposition. The role of inherited syndromes in cancer predisposition is outlined, and the concept of tumor suppressor genes is presented. Other pertinent issues are introduced, including risk, public health, and the social impact of presymptomatic genetic testing. The chapter serves as a pithy introduction to the entire work and is a helpful primer to the novice on this topic.
Chapter 2 reviews the principles of cancer screening in high-risk individuals, families, and populations. The ethical and legal issues related to cancer susceptibility and genetic testing are discussed in chapter 3, which includes insightful reviews of liability, confidentiality, vulnerability, employment and insurance discrimination, and patient rights to genetic knowledge. Chapter 4 addresses similar issues from a population perspective.
Chapter 5, on genetic counseling, is a well-organized, very thorough, and lucid discussion of genetic counseling issues pertinent to hereditary cancer. The chapter is a must for genetic counselors and physicians who deal with inherited cancer issues. Chapter 6 summarizes the integration of knowledge of inherited cancer risk into primary care practice.
Chapter 7 is an excellent review of the principles of genetic epidemiology and linkage analysis. The major cancer genes identified by linkage analysis are listed, as well as the available population-based cancer registries. Chapter 8 is a clearly written summary of the molecular methods used to identify specific genetic mutations. These two chapters are helpful primers not only for the genetics student but also for the practicing clinician to understand the reliability, limitations, and application of genetic tests in the clinical setting.
Part II begins with a chapter on cancers of the digestive system and nicely summarizes both the syndromes and the genes pertinent to digestive cancer susceptibility. Cellular mechanisms of relevant genes are also discussed, but clinical application of genetic knowledge and management of the syndromes is given only short shrift. Chapter 10 reviews the genetic epidemiology and relevant underlying susceptibility genes for cancers of the breast, ovary, and uterus. The BRCA1, BRCA2, and other susceptibility genes are discussed, including an insightful section on modifiers of susceptibility genes. A very helpful and clinically applicable approach to the screening and management of patients and families with inherited susceptibility to female cancers is given. Cancers of the urinary tract are the subject of the next chapter, with a review of the relevant inherited syndromes and some screening guidelines.
Chapter 12 deals with prostate and testicular cancers, their genetic heterogeneity, and the importance of the family history in screening for these malignancies. Neurofibromatoses and other neuro-oncological syndromes are discussed in chapter 13. The relevant syndromes and their genetic underpinnings are meticulously presented, but there are no clinical management or testing guidelines. Chapter 14 is a very complete, well-organized summary of the genetics of malignant melanoma. It includes an interesting history of discoveries, a description of the relevant mutations, and a summary of molecular pathophysiology. Genotype-phenotype correlations are discussed and candidate genes reviewed. Chapter 15 reviews nonmelanoma skin cancer. Chapter 16 addresses endocrine cancers, including the syndromes of MEN 1 and 2 and the MEN 1 and RET genes. The occurrence of mutations in these genes in sporadic tumors is also discussed, along with the relationship of RET mutations to Hirschsprung's disease. Clinical approaches to these diseases are presented, and additional rare endocrine syndromes are discussed.
Chapter 17 is devoted to tobacco-related cancers of the respiratory and upper digestive tract and includes a discussion of relevant genes, alleles, and observed mutations. Syndromes of abnormal DNA processing are discussed as a group in the next chapter, as well as the involved genes and biochemical consequences. A well-written chapter on childhood cancers and their genetic etiologies follows. The final chapter reviews recent developments and includes both social and ethical issues, as well as basic genetic discoveries.
The volume as a whole is a concise, well-written, and thorough review of the present knowledge of cancer susceptibility genetics. Most chapters include clinical guidelines to assist the practicing physician. The book is a must for genetic scientists and students of genetics at all levels and is also an important reference for practicing clinicians and genetic counselors, who must apply the knowledge of this rapidly expanding field to cancer prevention and patient and family management.
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