Familial context of genetic testing for cancer susceptibility: moderating effect of siblings' test results on psychological distress one to two weeks after BRCA1 mutation testing.

OBJECTIVES: To determine whether psychological distress differs among individuals tested for a BRCA1 mutation and is moderated by the pattern of their siblings' test results. MATERIALS AND METHODS: Participants in this study are members of a large kindred identified with a BRCA1 mutation. Subjects included 87 males and 125 females who completed a baseline interview, were tested for a BRCA1 gene mutation, received their results in person from a genetic counselor, completed a follow-up interview 1-2 weeks after the receipt of their test results, and had complete data on all variables used in the analysis. The main outcome of the study was psychological distress as measured by the Impact of Event Scale during the 1-2 week follow-up interview. Data were analyzed based on multiple regression. RESULTS: Male carriers, relative to noncarriers, experienced significantly more distress if they were the first tested than when all of their tested siblings were already known to be negative. Noncarrier males whose siblings all tested positive also encountered significant test-related distress. The largest adverse psychological consequences for female carriers, relative to noncarriers, were for those who were tested first and those whose tested siblings were noncarriers. CONCLUSIONS: The familial context in which genetic testing is conducted may be important for understanding how individuals react to their own test results.

Anencephalic infants as organ donors.

Transplantation technology has been refined in recent years and now offers hope to pediatric patients with a variety of end stage disease processes. The lack of available donors for the smallest potential organ recipients has led to the suggestion that anencephalic infants be used as organ donors. This suggested policy is contrary to current law and raises fundamental ethical issues relating to the definition of death and the treatment of the dying. The technical issues in the potential organ supply from this source are described and the opposing ethical positions developing in this debate are discussed.

Genetic testing, adverse selection, and the demand for life insurance.

The dramatic increase in genetic testing for adult-onset diseases has created a debate regarding whether or not insurance companies should be able to use genetic test results in underwriting. We use data from women who have been tested for the BRCA1 gene mutation along with data from otherwise comparable untested women to assess the potential for adverse selection in the life insurance market when tested individuals know their genetic test results but insurers do not. Our analyses show that women who test positive for the BRCA1 gene mutation do not capitalize on their informational advantage by purchasing more life insurance than those women who have not undergone genetic testing.

Attitudes toward the genetic testing of children among adults in a Utah-based kindred tested for a BRCA1 mutation.

Advances in molecular biology and genetics have led to the identification of the breast/ovarian cancer susceptibility genes BRCA1 and BRCA2, along with tests to detect mutations in these genes. Although the appropriateness of BRCA1/2 genetic testing for children has been debated in the literature, little is known about the attitudes of individuals who have undergone cancer susceptibility testing. The present study focused on attitudes toward BRCA1 testing for children among 218 adults from a Utah-based kindred who had received BRCA1 test results. Results indicated that approximately one-fourth of the participants would permit BRCA1 testing for children under the age of 18. General attitudes about genetic testing were predictive of attitudes toward the testing of children. In addition, men and individuals without a BRCA1 mutation were more likely to agree that minors should be allowed BRCA1 testing. Individuals whose mother had been affected with breast cancer were less likely to permit testing for minors. Among parents of minor children, less than one-fifth indicated that they would want BRCA1 testing for their own children; carrier status was not predictive of attitudes toward testing their own children. As breast/ovarian cancer susceptibility testing continues to be disseminated into clinical settings, there may be an increase in the number of test requests for minors. The findings of the present study represent an important step in exploring attitudes about genetic testing of children among individuals who have received cancer susceptibility test results.

Equitable distribution in pediatric heart transplantation. Arguments in favor of a national list.

The disparity between the supply and demand for pediatric donor hearts remains the major constraint in pediatric heart transplantation. This disparity draws attention to the importance of an equitable distribution policy for pediatric hearts. An examination of the policy on pediatric heart distribution shows that although a governmental task force recommended that these organs be allocated according to a national list, the current policy, developed by the United Network of Organ Sharing, emphasizes the local distribution of pediatric hearts. The decision to allocate organs locally was based on both theoretical and practical concerns about national distribution. In analyzing these concerns, we conclude not only that a national list may be a more equitable means of distribution but also that the arguments against a national list no longer justify a policy favoring local distribution. We suggest, therefore, that the time has come to reconsider implementation of a national list for pediatric heart distribution.

Prenatal screening: professional standards and the limits of parental choice.

Medicine has a strong tradition of respect for parental autonomy in reproductive decisions. As prenatal diagnostic technology develops, the physician's obligation to the prospective parents with respect to prenatal screening must be determined, and standards for disclosure of diagnostic capabilities and results must be developed. This article explores potential justifications for limits on parental choice in prenatal screening. Information about screening capabilities can be limited appropriately when resources do not exist to ensure accurate testing and counseling. Other policy limits to parental information and choice based on risk levels, cost-benefit analyses, or harms to the parent-child relationship cannot be established without broad consensus on complex ethical issues. Limits to parental choice may be more appropriately applied through the moral values of individual physicians in their provision of diagnostic services.

Selective abortion for familial Alzheimer disease?

Advances in human genetics will soon allow prenatal diagnosis of genetic conditions in the fetus that range from trivial to devastating. This commentary explores the concept of severity in genetic diseases and decisions regarding selective abortion. Familial Alzheimer disease is used as a model for the analysis of ethical issues raised by prenatal diagnosis and the subsequent termination of pregnancy. The genetics of the disease has yet to be elucidated, but this condition may be amenable to prenatal diagnosis in the near future, at least in some families. Abortion is a choice open to women in the United States; however, it is still desirable to discuss on purely ethical grounds pregnancy termination in the case of late-onset but severe diseases.

Psychological responses to BRCA1 mutation testing: preliminary findings.

The short-term psychological responses of 60 adult women tested for a BRCA1 gene mutation associated with a high risk of breast and ovarian cancer were investigated. Participants were members of a large kindred enrolled in an ongoing prospective study of the psychosocial impact of genetic testing. Initial results from participants who completed both the pretest baseline and the 1-2 week posttest follow-up interviews are reported. Gene mutation carriers manifested significantly higher levels of test-related psychological distress, as measured by the Impact of Event Scale, when compared with noncarriers. The highest levels of test-related distress were observed among mutation carriers with no history of cancer or cancer-related surgery. Although general distress (state anxiety) declined after testing, carriers were more distressed than noncarriers at follow-up.

Ethical issues and practical problems in preimplantation genetic diagnosis.

Author argues the preimplantation genetic diagnosis is ethically acceptable for currently intended uses, but a variety of ethical and practical issues will arise with further development of this technology.

Fetal privacy and confidentiality.

PIP: With the advent of new and better contraceptive methods and the ability to facilitate and manipulate fertilization and gestation, couples will gain greater control over their fertility. Once a pregnancy has been established or an in vitro embryo created, the ability to evaluate the embryo and fetus will increase dramatically with progress in human genetic research. Preconception and preimplantation genetic testing and screening are now possible, and the technology to perform prenatal screening early in gestation is advancing rapidly. Nonsurgical methods facilitate induced abortion with a relatively lower degree of trauma upon the woman undergoing the procedure. These capabilities may all be used to enable and even encourage the genetic selection of future children. Despite the ethical concerns associated with prenatal testing and abortion, these services will continue to be an integral aspect of reproductive medicine. As technology advances, however, it will be possible to test and screen for conditions which do not produce serious defects. Genetic conditions which produce relatively mild impacts upon health will be identifiable in the embryo or fetus, while late-onset conditions and genetic factors which have only a probability of affecting health will also be located in the fetal genome. Prospective parents may therefore soon have the capability of selecting their most desirable embryo in vitro, or terminating all undesirable fetuses in vivo until the preferred child is delivered. The medical profession must take some responsibility for establishing guidelines on the use of reproductive technology. The standards of practice for the medical profession must reflect the results of a broad social debate over competing moral values. The author develops an argument for legal and ethical limitations on the application of prenatal testing and screening technology, suggesting that for some medical conditions, respect for the privacy and confidentiality of the fetus outweighs parental rights to information about the fetus. Preliminary definitions for what constitute serious defects and minor conditions are developed.^ieng

The legal concept of wrongful life.

KIE: "Wrongful birth" suits are malpractice actions in which parents sue a physician for negligent conduct resulting in the birth of an impaired child. "Wrongful life" suits, which are more controversial, are brought on behalf of the impaired infant rather than the parents. Thus, the physician is sued, not for causing the impairment, but for negligent responsibility for the infant's very existence. After tracing the history of wrongful life cases in the U.S., Botkin analyzes the fundamental problems in the wrongful life concept in terms of the physician's alleged duty to the fetus and in terms of the concept of life as a harm. He urges rejection of this relatively new cause of action that threatens the judicial system's traditional respect for the intrinsic value of life.^ieng

The fire-safe cigarette.

Fires caused by cigarettes through the ignition of upholstered furniture and mattresses are a serious public health problem, accounting for more than 1500 deaths and 7000 serious injuries per year in the United States. Fire-resistant fabrics and stuffings, public education, and smoke detectors have had a limited impact on this problem. The federal government recently has completed a three-year study of possible modifications in cigarette design. The study has demonstrated the technical feasibility of product design changes that would substantially reduce the propensity of cigarettes to ignite fires. Legislation currently is pending in Congress and in three state legislatures to mandate a cigarette fire safety standard. This legislation deserves strong support by the medical profession.