Book Review

Inherited Susceptibility to Cancer: Clinical, predictive and ethical perspectives

N Engl J Med 1999; 340:1125April 8, 1999

Article

Inherited Susceptibility to Cancer: Clinical, predictive and ethical perspectives
Edited by William D. Foulkes and Shirley V. Hodgson. 456 pp. New York, Cambridge University Press, 1998. $95. ISBN: 0-521-56340-2

With an aging population and many infectious diseases now under control, cancer has become a major cause of morbidity and mortality in developed countries. Epidemiologic surveys indicate that the patient with cancer often has a family history of cancer. Familial cancers with a clear pattern of mendelian inheritance are very rare, and during the past decade most of the genes responsible for these rare disorders have been identified. The increased relative risk of cancer in family members of patients with cancer is probably due to the presence of cancer genes with low penetrance or of polymorphisms of genes with a role in metabolic pathways, combined with exposure to lifestyle or environmental risk factors. The identification of these minor but common cancer genes is the next challenge in the field of cancer genetics.

Since cancer is a common disease, many patients with cancer will have a positive family history. The recent discoveries of genes predisposing carriers to such common diseases as breast and colon cancer have attracted much attention from the media and have generated great expectations of genetic testing. Geneticists, clinicians, and family doctors are confronted by questions from patients for which there are no simple answers and for which a multidisciplinary approach is necessary.

Inherited Susceptibility to Cancer is a timely book that tries to provide some answers and guidelines. The book gives an up-to-date account of current knowledge about the cancer genes identified in the various familial cancer syndromes. (The final chapter includes important late-breaking developments that were reported after the completion of the other chapters.) It provides epidemiologic data and figures on increased relative risks in cases without clearly identified genetic causes and with a presumed multifactorial type of inheritance combined with variable sensitivity to environmental exposure. More important, it places “cancer susceptibility” in its proper social context. The contributors to the book are from various disciplines: clinical medicine, genetics, epidemiology, molecular biology, and genetic counseling.

The identification of “cancer genes” makes possible genetic testing and screening of populations for susceptibility to cancer. The absence of specific treatments or of adequate methods of prevention renders the benefit of such screening programs very questionable at this time.

The first part of the book deals with ethical, legal, and social issues, screening, and genetic counseling. The issues of public awareness, the benefits and dangers of screening, a patient's right to know the results of screening tests as well as the right not to know, protection of the individual and privacy, discrimination based on genetic information, genetic manipulation, and insurance and employment are discussed and placed in the appropriate context. Almost 50 pages (chapters 5 and 6) deal with the organization of genetic counseling in the cases of screening or detection of carriers in families at risk for cancer. Chapters 7 and 8 review the epidemiologic approach to finding genes and the molecular techniques applicable to analysis of gene mutations. This first part is essential because it puts the subject of cancer susceptibility in perspective and highlights the limitations of our current techniques and knowledge.

The second part of the book systematically outlines current knowledge of the inheritance patterns of many types of cancer, according to site, organ, or special group. These chapters cover most but not all types of cancer (hematologic cancer and soft-tissue sarcoma are not discussed). The chapters on cancer of the digestive system, the breast, the ovary, the uterus, and the endocrine organs are the most interesting, because of the recently well-characterized genes associated with each of these specific familial cancer syndromes. Genetic polymorphism is discussed in the chapter on tobacco-related cancers. The chapter on inherited abnormalities of DNA processing is also an excellent overview but will probably be difficult for many readers to understand. Childhood cancers are discussed in a separate chapter.

Each chapter deals with a collection of rare diseases or syndromes, and it is difficult to put the data regarding frequency and prevalence in perspective. A concluding chapter by the editors, presenting in tabular form a summary of the various cancer-susceptibility disorders, including information on the prevalence of each in absolute numbers and in percentages of cancers occurring at the same site as well as on the patterns of inheritance, would have been a valuable addition.

Inherited Susceptibility to Cancer should be of interest to geneticists, internists, oncologists, and surgeons, and also to interested family doctors. Each specialist will find general answers and a good introduction to a more in-depth study of a specific problem.

Anne Hagemeijer, M.D.
University of Leuven, 3000 Leuven, Belgium