Inherited Cancer Syndromes: Current Clinical Management
http://www.100md.com
《新英格兰医药杂志》
Advances in the field of genetics during the past 15 years have made possible the identification of a number of genes associated with an inherited predisposition to cancer. Genetic testing for susceptibility to cancer has thereby become a part of clinical practice. Susceptibility to cancers of the breast and colon, malignant melanoma, and other cancers, often in the setting of inherited syndromes, can now often be precisely defined by genetic testing in individual persons and families. The related issues of presymptomatic diagnosis and the prevention of disease have become particularly relevant, as have the proper application, interpretation, and use of genetic-test results.
(Figure)
Pseudocolor Diagram of Clustered Human Chromosomes inside a Dividing Breast-Cancer Cell Pulling Apart during Mitosis.
By permission of Paul J. Smith and Rachel Errington/Wellcome Photo Library.
Inherited Cancer Syndromes was specifically designed to educate physicians and health care workers about the genetic aspects, in the clinical setting, of inherited syndromes of cancer. The first half of the book addresses general issues such as the assessment of inherited risk, genetic counseling, and the ethical and legal issues raised by genetic testing. The second half reviews cancer-specific inherited risk and the individual cancer syndromes. There are chapters on breast cancer, colonic-polyposis syndromes, hereditary nonpolyposis colorectal cancer, ovarian and other gynecologic cancers, urologic cancers, and multiple endocrine neoplasias.
The first chapter is an excellent review of the assessment of inherited risk and includes general approaches as well as detailed descriptions of how to diagnose specific syndromes. The various models for determining the risk of breast cancer are also presented. The chapter would have been strengthened by the addition of information on the frequency at which mutations associated with various syndromes are found and the reasons why relevant mutations are not always found in patients known clinically to have a syndrome.
The chapter on genetic counseling reviews the history, principles, process, philosophy, and importance of this discipline in regard to clinical practice and genetic testing. The central counseling tenet of "nondirectiveness" — an approach sometimes neglected in settings where medical direction is usually given — is clearly presented. The specifics regarding the counseling visit and the items needed in the consent for genetic testing are outlined in detail. Although it is not discussed, the chief barrier to genetic counseling is financial reimbursement. Up to four hours of a counselor's time are needed for the assessment of risk and patient education. Yet no mechanism for reimbursement of these services exists in the U.S. medical system. Solutions are desperately needed in an environment in which clinical genetics is becoming an increasingly important part of the practice of medicine.
Ethical issues in regard to genetic testing for susceptibility to cancer are discussed in chapter 3. This chapter is possibly the best presentation of this topic available and is important reading for all clinicians who wish to understand clearly the unique issues involved in genetic testing. Three basic principles are discussed: beneficence toward the patient, respect for patient autonomy, and justice or fair treatment. These same principles could well be applied to most areas in the practice of medicine. Chapter 4 is an appropriate follow-up and succinctly reviews all sides of the legal issues that concern insurance, legislation, and privacy in genetic testing.
The chapters on syndromes are divided by type of cancer, and each includes discussions of risk assessment, indications for genetic testing, interpretation of test results, and integration into clinical management of risk estimates and results of genetic testing. The chapter on breast cancer also provides an insightful discussion of surrogate end-point markers. Each syndrome of susceptibility to polyposis and nonpolyposis colon cancer is described, with algorithms as to when genetic testing is indicated. Guidelines for prevention and management follow. The history and genetics of hereditary nonpolyposis colorectal cancer is particularly well outlined. Possible approaches to the prevention of ovarian cancer are given. The efforts to discover genes for familial urologic cancers are summarized, and, finally, genetic testing and the management of multiple endocrine neoplastic syndromes are presented. Missing from the chapters on specific cancers are discussions of inherited multiple melanoma and of nonsyndrome familial colon cancer; such a discussion is nicely presented in the chapter on breast cancer.
This book provides the knowledge base needed for most physicians to incorporate the principles of inherited susceptibility to cancer and genetic testing properly into their practices. It is highly, since many physicians and health care workers have not been trained in this area, which has become an established part of clinical medicine.
Randall W. Burt, M.D.
University of Utah School of Medicine
Salt Lake City, UT 84112(Edited by C. Neal Ellis. )
(Figure)
Pseudocolor Diagram of Clustered Human Chromosomes inside a Dividing Breast-Cancer Cell Pulling Apart during Mitosis.
By permission of Paul J. Smith and Rachel Errington/Wellcome Photo Library.
Inherited Cancer Syndromes was specifically designed to educate physicians and health care workers about the genetic aspects, in the clinical setting, of inherited syndromes of cancer. The first half of the book addresses general issues such as the assessment of inherited risk, genetic counseling, and the ethical and legal issues raised by genetic testing. The second half reviews cancer-specific inherited risk and the individual cancer syndromes. There are chapters on breast cancer, colonic-polyposis syndromes, hereditary nonpolyposis colorectal cancer, ovarian and other gynecologic cancers, urologic cancers, and multiple endocrine neoplasias.
The first chapter is an excellent review of the assessment of inherited risk and includes general approaches as well as detailed descriptions of how to diagnose specific syndromes. The various models for determining the risk of breast cancer are also presented. The chapter would have been strengthened by the addition of information on the frequency at which mutations associated with various syndromes are found and the reasons why relevant mutations are not always found in patients known clinically to have a syndrome.
The chapter on genetic counseling reviews the history, principles, process, philosophy, and importance of this discipline in regard to clinical practice and genetic testing. The central counseling tenet of "nondirectiveness" — an approach sometimes neglected in settings where medical direction is usually given — is clearly presented. The specifics regarding the counseling visit and the items needed in the consent for genetic testing are outlined in detail. Although it is not discussed, the chief barrier to genetic counseling is financial reimbursement. Up to four hours of a counselor's time are needed for the assessment of risk and patient education. Yet no mechanism for reimbursement of these services exists in the U.S. medical system. Solutions are desperately needed in an environment in which clinical genetics is becoming an increasingly important part of the practice of medicine.
Ethical issues in regard to genetic testing for susceptibility to cancer are discussed in chapter 3. This chapter is possibly the best presentation of this topic available and is important reading for all clinicians who wish to understand clearly the unique issues involved in genetic testing. Three basic principles are discussed: beneficence toward the patient, respect for patient autonomy, and justice or fair treatment. These same principles could well be applied to most areas in the practice of medicine. Chapter 4 is an appropriate follow-up and succinctly reviews all sides of the legal issues that concern insurance, legislation, and privacy in genetic testing.
The chapters on syndromes are divided by type of cancer, and each includes discussions of risk assessment, indications for genetic testing, interpretation of test results, and integration into clinical management of risk estimates and results of genetic testing. The chapter on breast cancer also provides an insightful discussion of surrogate end-point markers. Each syndrome of susceptibility to polyposis and nonpolyposis colon cancer is described, with algorithms as to when genetic testing is indicated. Guidelines for prevention and management follow. The history and genetics of hereditary nonpolyposis colorectal cancer is particularly well outlined. Possible approaches to the prevention of ovarian cancer are given. The efforts to discover genes for familial urologic cancers are summarized, and, finally, genetic testing and the management of multiple endocrine neoplastic syndromes are presented. Missing from the chapters on specific cancers are discussions of inherited multiple melanoma and of nonsyndrome familial colon cancer; such a discussion is nicely presented in the chapter on breast cancer.
This book provides the knowledge base needed for most physicians to incorporate the principles of inherited susceptibility to cancer and genetic testing properly into their practices. It is highly, since many physicians and health care workers have not been trained in this area, which has become an established part of clinical medicine.
Randall W. Burt, M.D.
University of Utah School of Medicine
Salt Lake City, UT 84112(Edited by C. Neal Ellis. )