ELSI Publications and Products Database

This pilot project will invite adult members of classic and variant Li-Fraumeni families at 50% risk of carrying an altered p53 gene to participate in a program in which they could be made aware of their p53 status. We will assess the expectations and motivations of at-risk adults and their partners for participation in a program of predictive testing. We will explore their psychological preparedness to participate, and, after disclosure of results, will evaluate the impact of the knowledge of their p53 status on their psychological well-being and family relationships. We will assess their understanding of genetic information, and will provide extensive genetic counseling regarding relevant choices and their implications through the process. We will explore with them the readiness of subjects who are parents and prospective parents to enter their at-risk children into a predictive testing program were it to exist, and what features of such a program might be important to families. We will also assess the receptiveness of the population to advice regarding disease surveillance and risk avoidance. We will conduct this program with full cognizance of the complex ethical and social issues which are inextricable from this work.

This project will evaluate a BRCA1 predisposition testing program modeled closely on the Huntington Disease paradigm for members of previously identified families in which cancer susceptibility has been linked to BRCA1 with posterior probability >90%. Although we anticipate the cloning of BRCA1 before or during the project, we will restrict participants to members of linked families because of the limitations of available risk information which has been derived from linked families only (1,2). In this project, we will develop, implement and evaluate a program in which we will train and supervise genetic counselors and nurses to administer pretest education and disclosure counseling for BRCA1 susceptibility to members of linked families in their local communities. We will observe the psychosocial effects of genetic testing for risk of breast and ovarian cancers in members of these BRCA1-linked families. We will describe the impact of participation in a predisposition testing program with regard to quality of life and cancer risk management health behaviors. We will also provide an education intervention to the health care providers of female relatives regarding medical management and genetic privacy implications of heritable cancer risks, and will assess the impact of the intervention on provider knowledge and recommendations for risk management.

The genes conferring increased susceptibility to breast and ovarian cancer, BRCA1 and BRACA2, were identified in the mid-1990's and commercial testing became available soon thereafter. Intensive evaluation of women undergoing testing for BRCA1/2 germline mutations has been conducted, and has demonstrated that women participating in genetic testing through highly structured and supportive programs conducted largely at academic institutions have generally done well through the process and in the long term (1-5). In the United States, the vast majority of BRCA1/2 testing is now performed by a single commercial clinical laboratory {Myraid Genetics Laboratory (MGL}, with the test available to women directly through their physicians. A substantial portion of testing is now accomplished through this mechanism, but the extent to which clinical testing as it is now performed approximates the intensive support provided in the structured research programs is unknown. The outcomes of women tested clinically outside of academic centers have not yet been studied. In this project, we intend to explore three areas in which data have been lacking, using the unique resource of the unselected population of women tested through MGL. These include: 1) What are the outcomes (knowledge, psychological adjustment, health behaviors, satisfaction, and confidentiality concerns) of women undergoing testing across the spectrum of clinical settings in which testing is carried out? 2) Are specific characteristics of providers (experience, expertise, use of genetic counselors) and of the circumstances in which testing is provided (academic, non-academic, specialty vs. course of clinical practice) associated with more favorable outcomes for women undergoing testing? and 3) What are the factors that distinguish physicians who are ordering BRCA1/2 genetic testing from those who have not utilized this new technology? The project involves surveys of women who have provided specimens to MGL for BRCA1/2 analysis, their providers, and control physicians. The information learned from this project may help to create a standard for the optimal conduct of BRCA1/2 testing, and potentially for other predisposition testing as well.

Genomic biobank research, like much scientific and biomedical research, aims to produce generalizable knowledge of collective benefit to humans and possibly other living organisms. Direct benefit to individual participants is not a paramount goal, if a goal at all. But this raises ethical concerns. Biobank research may uncover medically significant information. Some have argued that there is an ethical duty to inform individual participants of such findings. In this project, I will develop a presumptive case against returning any individual results to subjects in biobank research. First, I will critically examine the claim that it is morally obligatory to disclose individual results. Utilizing the framework of negative and positive duties, I will explore the philosophical foundations of five different principles that might underwrite such a duty - non-maleficence, respect for persons, beneficence, reciprocity, and the duty to warn or rescue. While these principles are often cited in the debate, little attention has been given to philosophical complexities or qualifications. Considered with more rigorous scrutiny, each principle fails to support a moral obligation to return individual results. Second, I will critically examine the weaker claim that, even if it is not obligatory, returning at least some individual results would be morally good or at least morally permissible. Against these more moderate claims, I will explore how returning individual results in biobanking would disproportionately burden limited research resources and introduce at least six significant costs and risks. A policy of never returning results would reduce or eliminate all six of these costs and risks and outweigh the potential benefits of even selective returns of individual results. Finally, I will identify and consider potential solutions for any significant practical challenges that might be encountered when individual results are not returned. Given that some participants will desire access to these results, and others may implicitly expect to receive them, careful consideration needs to be given as to how to ethically and effectively communicate to potential research participants the rationale for withholding all individual results. Additionally, there will be important questions about how this rationale can be operationalized within the informed consent process. I will consider these and other challenges and offer recommendations about how best to meet them. PUBLIC HEALTH RELEVANCE: This project will critically examine the claim that researchers in large biorepositories have an ethical duty to inform participants of at least some individual results. To do this, I will first analyze the basis for thinking that any actions are morally obligatory or morally good and then apply this to the unique situation of biorepository research. I will develop an argument against returning any individual results to study subjects and recommend policies and regulations for effectively putting this into practice.

The Navajo Nation placed a moratorium on genetic research studies in 2002, yet the tribe has high rates of genetic diseases and disorders. Historical distrust, fears of exploitation, and limited understanding of genetic research have played a role in the placement of the moratorium, yet no formal studies have been carried out to date to identify the key concerns, needs and desires of the Navajo regarding genetic research. Seven years after the issuance of the moratorium on genetic research, it is not clear whether a more permanent research policy will be developed, what it would look like, or whether attitudes of members of the Navajo Nation and policy makers have since changed. Although the Navajo Nation has a unique legal status, the concerns and attitudes towards genetic research among its members reflect, to some extent, more general issues about the relationship between biomedical scientists and participants in human subjects research, including the meaning of individual informed consent, community consent and engagement, the advent of patient advocacy and the experiences of individuals with rare diseases or common diseases like Type 2 Diabetes. Specific Aim 1: To map the context and ethical issues around the moratorium on genetic studies: Several key individuals such as physicians, scientists, political leaders, and Navajo medicine men were instrumental in informing the NNHRRB in enacting the moratorium on genetic studies. I will examine documents and interview individuals in order to map the ethical and cultural issues around the moratorium on genetic studies. Specific Aim 2: To interview Navajo individuals on the current attitudes and opinions related to genetic research: The larger Navajo community was not actively engaged in the conversation on genetic studies and the moratorium. After the moratorium was put in place, it was not publicized very widely, so the level of current knowledge about it is unknown. Describing the landscape of often competing views on the moratorium will be a central theme of my proposed research on attitudes toward genetic studies. The impact of this research project could have implications for genetics and formal policy on genetic research studies on the Navajo Nation or in other indigenous groups. PUBLIC HEALTH RELEVANCE: The moratorium on genetic studies limits the opportunities for the Navajo Nation to benefit from genetic research. However, important cultural and political issues need to be discussed and shared before a formal research policy can be developed. This project will explore the ethical, legal, social, and cultural issues of the Navajo in regards to genetic research.

Candidate Dr. Nanibaa' Garrison is an Assistant Professor at Vanderbilt University on the tenure-track in the Center for Biomedical Ethics and Society with a primary appointment in the Department of Pediatrics and a secondary appointment in Anthropology. She completed a Ph.D. in genetics at Stanford University and postdoctoral fellowship at the Center for Integration of Research on Genetics & Ethics (CIRGE) within the Stanford Center for Biomedical Ethics (SCBE) with the support of an NIH F32 postdoctoral fellowship. During the five years of this career development award, she plans to gain expert level knowledge in the ethical, social, and cultural implications of genetics research, with a particular focus on community engaged research with American Indian stakeholders. Her long-term goal is to conduct an independent research program where she becomes a trusted intermediary who understands science, research ethics, and cultural concerns involving the inclusion of minority populations in genetics research, including issues on biobanking and clinical trials. She seeks to pursue an academic career, bridging academia with community-engaged research, to emerge as a leader working with tribes and minority communities to ensure ethical engagement with research. She proposes strong mentorship and a relevant career development plan that will enable her to successfully compete for independent funding through R01 grant mechanisms. Environment Dr. Garrison has assembled a mentorship team who can provide her with complementary areas of expertise. Ellen Wright Clayton, MD, JD, Professor of Craig-Weaver Professor of Pediatrics and Professor of Law, and co-Founder of the Center for Biomedical Ethics and Society at Vanderbilt University is her primary mentor and provide guidance on the ethical and policy issues in genomics. Wylie Burke, MD, PhD, Professor of Bioethics and Humanities at the University of Washington, will provide mentorship on the ethical and cultural issues in genomics and will provide guidance for engaging communities in research. Mary S. Dietrich, PhD, Professor of Statistics and Measurement in the Schools of Medicine (Biostatistics, Ingram Cancer Center, Psychiatry) and Nursing at Vanderbilt University will provide mentorship on conducting survey research and statistical analyses. With the enthusiastic support of her mentors, Center for Biomedical Ethics and Society, and institutional support, Dr. Garrison is well prepared to complete the training and studies in this proposal and develop into a successful academic investigator. Research This proposal aims to characterize the views and opinions of American Indian/Alaska Native/Native Hawaiian (AI/AN/NH) stakeholders, including tribal leaders, scientists, clinicians, and policy makers, on genetic research in order to develop guidelines, strategies, and policies for tribes to engage in ethically sound genetic research. Aim 1 will incorporate qualitative data through semi-structured interviews coupled with quantitative data obtained through surveys to provide a basis for tribal leaders and an Advisory Board to guide and shape policies that will reframe the debate about genetics and genomics. Aim 2 will bring a group of stakeholders together to deliberate, using the Delphi process, about priority areas requiring additional guidance for policy making. The results obtained will guide policy-making and the creation of guidelines for the ethically and culturally acceptable conduct and implementation of genomics research for tribes to consider for adoption. PUBLIC HEALTH RELEVANCE: This project will explore the ethical, social, and cultural issues of the American Indians in regards to genetic research. Engaging tribal leaders and relevant stakeholders such as scientists, clinicians, and policy makers on issues around genetic research will create a more complete understanding of these challenges and enable them to create policies that may permit greater participation by American Indians and their tribes.

This proposal addresses the question posed in the RFA for the ELSI program 'Will continuing research in molecular biology and functional genomics affect how individuals and society view the relationship of humans to one another and to the rest of the living world?' Specifically, the purpose of this application is to address the impact of current and future knowledge of genetics and genomics on the scientific and cultural definition of race, an issue for the Human Genome Project (HGP). Results from increased knowledge about human gene sequences has led to the conclusion that division of the species according to racial lines is artificial, arbitrary and lacking in biological meaning. At the same time such information has demonstrated that at numerous loci, there is wide variation between allele frequencies in the total human population, and such variation is particularly obvious when comparing different racial groups. The purpose of this proposal is to develop scientific and philosophical tools to address and clarify the apparent racial genetics paradox, to better define the categorization of humans according to DNA sequence characteristics, and to provide more useful categories with respect to human genetic diversity as applied to biomedical research and clinical applications. It is anticipated that the results of these efforts will be of benefit in the new atmosphere of genome based definitions of individual characteristics. The specific aims are: to perform a thorough and complete analysis of the current published biomedical literature on genetic variation as a function of race or ethnicity combined with current and future data from the HGP, and other related projects. A new paradigm of gene-specific variation will be developed for a biomedically useful method of division of the human population into groups based on criteria different from current definitions of race.

Thai-U.S. Drug Dependence Genetics Research Training Program (DDGRTP) Drug dependence constitutes a global public health problem of enormous economic, social, and medical cost to the international community. Developing countries, in particular, are disproportionately affected, due to both the economic incentives associated with the production of illicit drugs, and the less well-established institutional infrastructure (i.e., facilities and personnel) dedicated to the understanding, treatment and prevention of drug dependence disorders. In this application, we propose a collaborative research training program in the genetics of drug dependence, between Faculty of Medicine, Chulalongkorn University in Bangkok, Thailand (the leading medical research center in Thailand) and the Yale University School of Medicine in the U.S. Three major training mechanisms are proposed for Thai trainees, including long-term (2-yr) predoctoral and postdoctoral fellowships, and brief (3-month) mini-fellowships. We also propose one minor (1-month) 'field' exchange training rotation for U.S. trainees with an interest in international collaborative genetics research to study in Thailand. The present training program builds on an extensive research program in genetics of drug dependence at Yale University School of Medicine, and on existing collaborations between investigators at Yale and investigators at Chulalongkorn in the study of drug dependence in Thai population isolates. The program will contribute to the capacity of investigators at Chulalongkorn to conduct state-of-the-art research in genetics of substance dependence through a range of training experiences; and also to contribute to the capacity of Yale investigators to conduct research in Thailand with Thai collaborators, through increased interaction with Thai counterparts. Eventually it will allow us to build, as specified in the RFA, 'a critical mass of scientists, health professionals and academics with human genetics expertise and a sustainable research environment at the collaborating developing country institution.' The training grant is also specifically designed to serve a major public health purpose by enhancing Thailand's capacity to confront an epidemic of drug dependence that is unprecedented in its history.

This study will explore the process by which families at increased risk of adult-onset disease decide to involve their children in research on genetic susceptibility. Through interviews with parents at increased risk for heart disease and breast cancer, their children between the ages of 10 and 17, and the physicians they identify as influential, this study will explore perceptions about the motivations and barriers to participation of children in research on genetic susceptibility to these two diseases. In addition to comparing two diseases, the study will compare families from different cultural backgrounds (African-American, Jewish and Caucasian non-Jewish) and children at different stages of cognitive development. Follow-up family interviews will be conducted one year after the initial interview. The results of these qualitative interviews will be used to develop criteria for assessing the adequacy with which recommended elements of consent and assent for children's participation in disease susceptibility protocols have been addressed.

This study will analyze the process of publicizing new genetic discoveries, and the impact of medical reports on consumers and providers. Under specific aim 1 (SA1), the investigators will conduct individual interviews of scientists and journalists to explore the reasons they publicize genetic discoveries, their views of the impact of their stories, the means scientists use to bring their discoveries to public attention, what information about genetic discoveries they believe is important for the public to know, and the efforts journalists make to assure the quality and prominence of their stories, and the obstacles they encounter. Under specific aim 2, the investigators will develop a checklist for assessing the accuracy, balance, and context (ABC) of stories emanating from discoveries made after this study begins. This checklist will be based on the views of scientists and journalists from SA1, analysis of previously published press releases and stories, and the opinions of consumers (obtained through a focus group) about what is important to them. Using the checklist, the investigators will analyze stories that appeared before and after the study begins and explore the effect of a variety of factors, on ABC. Under specific aim 3, the investigators will prospectively examine the response of consumers and providers to specific discoveries reported in the media. Through questionnaires and brief and in-depth interviews, the investigators will establish how frequently they call a health care facility in response to a specific story, which story it was and what components of the story were salient in their decision to seek more information about the test or therapy that was mentioned in the story, and whether the ABC and prominence of those stories are related to impact on the public. The investigators will explore the characteristics that distinguish those who called a health care facility and those who did not call (a comparison group). Under specific aim 4, the investigators will feed back their findings individually to the scientists and journalists who participated under SA1, and then convene a more diverse panel of both groups to help develop recommendations for improving the coverage of stories dealing with genetic discoveries so that consumers' and providers' responses to such reports can be more informed.

Genetic service providers interact with patients who are experiencing profoundly personal and emotional life events. Many interactions occur at the time of diagnosis of a serious or life-threatening disorder in a fetus, child or adult. Other interactions occur over the course of providing on-going care to genetically affected individuals, including care rendered near the end of life. In a recent NIH workshop on end-of-life-issues in genetic disorders, there was consensus that genetic service providers need to find ways to talk about end-of life issues with their patients, and help patients deal with uncertainty. It is likely that genetic service providers experience considerable grief, moral distress and threats to integrity in the course of caring for individuals and families affected by, or at increased risk of, serious genetic disease. There is even some evidence that moral distress can lead to professional burnout. Yet this distress has rarely been acknowledged or described in the literature, nor have most genetic service providers received adequate training in any of these areas. The proposed study will examine, both quantitatively and qualitatively, the nature, extent, sources and consequences of distress among different types of genetic service providers, and develop recommendations regarding the sort of intervention that might be developed to help providers deal with their distress. Under specific aim 1 (SA1), we will conduct 3 focus groups, 1 of genetic counselors, 1 of genetic nurses and 1 of clinical geneticists, to explore the nature of distress and suffering (moral distress, grief, threats to integrity, uncertainty) that they have experienced in their work. Under SA2, we will administer a questionnaire to a larger sample (N=300) of genetic service providers (100 of each type) who care for individuals with potentially life threatening conditions in prenatal, pediatric and adult genetics clinics, and conduct in-depth telephone interviews of 90 questionnaire respondents (30 of each type) to determine the variability in sources and extent of distress among different types of genetic service providers, the consequences of the distress experienced by each and the kind of intervention that they would find most useful. Under SA3, based on previous input as well as input from one mixed focus group, we will develop recommendations for an intervention to reduce distress experienced by genetic service providers. Such an intervention would be aimed at renewing commitment to the profession and improving patient care.

In this project a random sample of 60 young obstetric providers in Maryland and 10 pregnant women age 33 and over per provider (nested design) will be selected to accomplish three goals. First, we will audiotape the initial prenatal visit of all 600 patient-provider pairs to improve our understanding of various elements of communication about prenatal genetic testing, in comparison to communication about non-genetic issues. Elements will focus on ethical considerations including provider directiveness, the accuracy and completeness of information disclosed, and attention to confidentiality. Gender and educational differences in provider communication will be assessed by comparing male obstetricians with female obstetricians, and female obstetricians with nurse midwives (20 providers in each group). Tapes will be analyzed using the Roter Interaction Analysis System. Next, we will interview patient participants to assess the impact of that communication on their satisfaction, and on their testing decisions. Finally, we will conduct in-depth interviews of providers to determine what factors contribute to variation in provider communication, including the nature of their patient population, their attitudes toward genetic testing and abortion, their perceived role responsibility in communication and decision-making about genetic testing (with regard to disclosure, directiveness and confidentiality), their awareness of established guidelines for offering testing, their confidence in communicating about genetic information, their practices of referral for genetic counseling, and their concerns about/experience with legal liability. Results will have implications for the utilization of current and future prenatal genetic tests, the education and training of obstetric providers regarding prenatal genetic testing, and the quality of the decision-making process.

This study will develop, implement and evaluate a model informed consent (IC) process for genetic testing for breast cancer that integrates the perceptions of consumers and providers. The model IC process will address both content and style of disclosure and counseling. The study will develop and utilize surveys of providers and consumers to determine the knowledge, expectations and perceptions of both groups of genetic testing for breast cancer. After examining discrepancies between and among groups of consumers and providers, model educational materials will be developed for the IC process that reflect the expectations of consumers and providers. A pilot BRCA1 testing program will be implemented that incorporates the content of disclosure appropriate for each category of patient, and randomizes 140 female and male patients who are eligible and interested in BRCA1 testing to one of two disclosure styles: individual or group pre-test education and counseling. We will evaluate both the content and style of our model IC process in terms of patient knowledge, satisfaction, perceived decision-making autonomy and testing decisions. Our findings will have implications for the offering and utilization of genetic testing for breast and ovarian cancer, and for the development of IC guidelines, and will point to necessary improvements in medical training with regard to consent for predictive testing.

This project will first identify and analyze a series of specific ethical concerns or questions that have, or will arise as a consequence of the HGP, including genetic screening and diagnosing genetic disorders or predispositions, privacy, ownership, and security of HGP data, and genetic variations within and between groups. These concerns will be analyzed in the context of morally relevant variables that emerge from the application of a formal moral theory. Analyses based on the application of other moral theories will be done to control for unintentional biases. The research team will apply a formal set of moral rules in order to establish relevant variables that permit a distinction between morally acceptable and unacceptable policy alternatives, in order to address the ethical concerns and questions that are likely to arise in considering policy alternatives relating to the knowledge and information acquired by the HGP. Finally, a series of mechanisms for informing and involving the various constituencies in a discussion of issues and policy options will be examined. These include research articles, a book, and summer workshops.

The University of Utah Human Genome Center is proposing the creation of a core center for the study of the ethical, legal and social issues in human genetics. A multidisciplinary faculty will organize and conduct five activities as part of the core: 1)'Guidelines for Genetic Research in Families' will be prepared for use by IRB's, investigatory and research subjects on the ethical, legal, and social issues that arise in genetic research with families; 2) a'Fellowship Program' will be developed for two fellows per year; 3) a University ;'Seminar Series' will continue our intramural program of multidisciplinary seminars focused on the applications of contemporary genetic research; 4) an 'Ethics Forum' will continue to provide an opportunity for the discussion of contemporary issues by the young scientists involved in genetic research; and 5) 'Public Education' in the ethical, legal, and social issues in human genetics will be conducted through a collaboration with the Education and Outreach Core. The Utah ELSI core will be a strong, long term program of research and education on ELSI issues that will provide valuable support for investigators and subjects involved in human genetic research.

The disability rights critique of prenatal testing asserts that genetic decision-making occurs in a context of misinformation and devaluation regarding the lives of people with genetic and/or prenatal diagnoses and that health professional attitudes reinforce this bias. This is a three-year project designed to explore the areas in which medical genetic advising is, or is not, informed by the lived experience of persons with genetic and/or prenatally diagnosable disabilities. The project will be informed throughout by an Advisory Panel of scholars, professionals, bioethicists, and activists prominent for their work on genetics. The first study uses in-depth interviews to explore the views of genetic counseling professionals, medical specialists, persons with genetic and/or prenatally diagnosable disabilities, and parents of individuals with genetic disabilities (Perspective Informants) regarding issues of life with genetic disability, genetic services, social and professional attitudes toward disability, and determinants of "quality of life." The second study involves the broad national distribution of a questionnaire eliciting opinions on genetics and disability from the stakeholder groups listed above. The objectives of this research are to: —> Examine health professionals' views - Investigate knowledge and beliefs about life with genetic disabilities (and related social issues of genetic decision_making) of professionals who apply human genome information to clinical decision_making with patients/clients; —> Examine the views of persons living with genetic disabilities - Collect information from persons with genetic conditions and parents of persons with genetic disabilities about their experience of life with disability and their views on genetic decision_making in social context; —> Determine areas of agreement, conflict, and gaps in knowledge - Compare information gathered from the respective stakeholders referenced in Goals I and 2 to determine areas of agreement, areas of conflict, and gaps in perspectives; —> Develop useful recommendations for providing more informed professional training, clinical practice, and policy.

The goal of the proposed research training program is to strengthen the capacity of Venezuelan scientists based at the University of Zulia to study genetics of common hereditable disorders relevant to Latin America and the Caribbean, and in particular to Venezuela. The strategy is to enhance the current research and training programs at the University of Zulia by: (1) training a critical mass of scientists and engineers in the design and conduct of modern genetic/genomic research (2) facilitating the development of a research and training infrastructure at the University of Zulia that will draw upon and focus clinical and scientific expertise throughout Western Venezuela (3) sustaining the research and training programs at the University of Zulia by establishing collaborative networks with Columbia University researchers studying the genetic basis of the most common complex hereditable disorders. The proposed training program seeks to capitalize upon current genetic and genomic research programs at Columbia University that overlap thematically with the focus on common heritable neurodegenerative disorders at the University of Zulia. The training program is designed to educate doctoral students and postdoctoral fellows in human genetics, including genetic epidemiology, population genetics, molecular genetics, clinical genetics, statistical genetics and bioinformatics, with a broad understanding on the ethical, legal and social issues related to human genetics research. The didactic component of the program includes a series of academic courses, seminars and laboratory rotations. In the research component each Fellow will work closely with a Preceptor on an independent research project of the Fellow's choosing and that is related to his/her future research in Venezuela. In addition Fellows will be exposed to the process of development of low-cost diagnostic methods that may facilitate the recognition of neurodegenerative disorders and the development of preventive or ameliorative treatment options. At the end of the program Fellows should understand the critical aspects of study design, methodology, and genetic and epidemiological theory relevant to the detection of complex disease loci and to specifically address the interaction of genetic factors with environmental and cultural factors. Emphasis will be given to defining tractable genetic targets and building productive collaborations.

This study aims to identify ethnocultural and psychosocial factors related to intentions to obtain genetic testing for heritable forms of colon cancer in increased-risk and control adults of Caucasian, Japanese, and Hawaiian ethnicity who are living in Hawaii, and identify and describe ethical and social issues and attitudes that may affect intentions to offer genetic testing for colon cancer among health professionals in Hawaii. The first part of the study uses case-control methodology. We will use a mail questionnaire to survey first-degree relatives (FDRs) of patients diagnosed with colon cancer (n=750) and FDRs of age, sex, and ethnicity-matched population-based controls living in Hawaii (n=750). The second part of the study will survey physicians (n=875) and nurses (n=875) in Hawaii through mailed questionnaires. The survey will examine factors influencing intentions to offer genetic testing for cancer, including personal and practice characteristics, views about ethical and social-legal issues, and attitudes toward genetic testing. This study is unique and timely because of its multiethnic population, the use of case control methodology, and the potential to establish a foundation for planning culturally appropriate and effective counseling programs related to genetic testing for cancer.

This project builds on an exploratory study of psychosocial and ethnocultural factors related to intentions to obtain genetic testing for heritable colon cancer, and a pilot study of genetic counseling for intermediate-risk colorectal cancer (CRC) family members. The specific aims of the study are to: (1) evaluate the impact of a culturally sensitive program of Colon Cancer Risk Counseling (CCRC) on: a) adherence guidelines for early detection of CRC, b) comprehension of personal CRC risk, and c) psychological adaptation to familial cancer, among individuals with family history of CRC; (2) evaluate the impact of CCRC on subgroups of persons at different levels of risk, various ages and educational levels, males vs. females, and persons of different ethnic groups; and (3) examine the extent to which risk comprehension and psychological adaptation mediate the impact of CCRC on adherence to screening. Subjects will be 700 siblings and children, aged 40 and over, who have a positive history of CRC in one first degree relative.

PROJECT SUMMARY/ABSTRACT Living donor kidney transplantation (LDKT) is promoted to redress the shortage of kidneys for transplantation. However, studies show that living donors (LDs) have a greater risk of kidney failure than healthy non-LDs post-donation.4-6 Moreover, African American (AA) LDs have an even greater risk of kidney failure post-donation than European American (EA) LDs.4,5 These findings have generated heightened concerns in the transplant community over protecting LDs' safety and improving LDs' informed consent.7-14 Genetics may help explain this disparity. Genetics research found that Apolipoprotein L1 (APOL1) gene variants (1-2 alleles) are significantly associated with kidney failure predominantly in AAs.15-19 Kidney transplants from deceased donors with APOL1 variants had significantly shorter survival than kidneys from donors without variants.20 APOL1 variants may explain why AA LDs have a greater risk of kidney failure post- donation than do EA LDs.5,6,20 Thus, testing AA potential LDs for APOL1 variants could better risk stratify them. Little is known about the transplant community's attitudes about and practices of integrating APOL1 genetic testing into the routine clinical evaluation of AA LDs. No guidelines exist for genetic testing in transplantation. While proponents believe that the evidence is strong enough to warrant APOL1 testing,21,22 critics counter that testing is premature.23 Yet some transplant centers are using APOL1 testing routinely,22 or on a case-by-case basis. Transplant centers' practices are ethically charged: (not) using APOL1 testing could harm AA LDs. LDs unknowingly with the variants might make less informed decisions and unnecessarily undergo donation, which would violate the ethical principle of non-maleficence, as LDs gain no direct medical benefit from donation.25-27 Conversely, by learning they had APOL1 variants, LDs may choose to not donate to protect themselves or prevent the recipient from getting a kidney with potentially lower graft survival. Testing may also affect AAs' cultural identity, which in turn could shape attitudes about LDs' willingness to use APOL1 testing. The objective of this study is to assess the ethical and sociocultural implications of physicians' use of APOL1 testing for AA LDs, and to develop culturally sensitive educational materials for genetic counseling about APOL1 testing. We will assess the transplant community's normative expectations, attitudes, and current practices about testing AA potential LDs for APOL1 variants through a national survey. We will also assess AA LDs' information preferences, attitudes about, and willingness to be tested for APOL1 variants through semi-structured interviews. The results will inform the development of culturally sensitive education materials for genetic counseling about APOL1 testing, which will be refined by focus groups with AA LDs. The proposed study is timely because APOL1 testing could increase AA potential LDs' safety and reduce disparities in AA LD outcomes. This study facilitates NHGRI's initiative to better understand the implementation of emerging clinical genomics into clinical practice,32 consistent with the NIH's precision medicine's initiative.33

Although scholars have offered valuable policy recommendations, lawmakers lack a source of comprehensive, clear, and unbiased research concerning the ethical, technical, and legal issues that influence genetics legislation. This project is intended to provide legislators with objective and comprehensive information from a nonpartisan source so they can draft genetics-related legislation that accurately conveys the legislative intent; is clearly understood by lay people, scientists, and industry; and avoids unintended adverse effects. To achieve this goal, the project will analyze legislation and the legislative process to identify trends, difficulties, lack of uniformity of approaches, and inconsistencies with legislative intent, sound science, and ethical principles. Specifically, the project will track and collect proposed and existing genetics legislation in the nation's 50 states, including that related to the health-care and public health systems, insurance, employment, research, criminal justice, paternity, adoption, and any other legislation, regulations, or case law that significantly relate to human genetics. In addition, the project will survey and interview legislators who draft genetics legislation. Moreover, to inform legislators of relevant scholarly literature, the project will gather, analyze, and disseminate current literature on genetics and genetics-related law, ethics, and public-policy issues. Finally, the project will provide a forum for state legislators to discuss genetics law and related policy issues to encourage a more consistent and uniform approach to regulation of genetic information and technologies. The overall objective of the project is to educate legislators about genetics--science, law and ethics--through reports, articles, a Website homepage, and a National Conference. These educational means should give legislators the tools to craft genetics-related statutes that: 1) achieve intended legislative and policy goals; 2) are scientifically and ethically sound; 3) protect privacy interests and prevent discrimination; 4) are comprehensible to the lay, scientific, and commercial communities; and 5) avoid unintended burdens on research, medical treatment, and human rights.

The purpose of this project is to develop models for broad-based community dialogue to examine the value and ethical dimensions of emerging technologies in applied human genetics. The project will be carried out by a multidisciplinary and multi-institutional team with expertise in ethics, science policy, and education. The Center for Applied and Professional Ethics at the University of Tennessee, joins with an unusually science-literate congregation to develop this project. The focus will be guided by the report of a task force of the United Methodist Church which has held extensive hearings on these matters throughout the country. Anticipated results include: a videotape and handbook/curriculum for follow-up discussions, and a follow-up project to carry this inquiry into high school curricula throughout Tennessee.