Attitudes Toward Updated Genetic Testing Among Patients with Unexplained Mismatch Repair Deficiency

Individuals who have colorectal cancer (CRC) or endometrial cancer (EC) displaying loss of immunohistochemical (IHC) staining of one or more mismatch repair (MMR) proteins without a causative germline mutation are said to have unexplained mismatch repair deficiency (UMMRD, also known as mutation-negative Lynch syndrome). Comprehensive genetic testing that could potentially further clarify Lynch syndrome (LS) carrier status is essential to provide tailored screening guidelines to affected individuals and their family members; however, patient understanding of the potential impact of updated genetic testing for LS is unclear. This study aimed to evaluate the interest in and perceived impact of updated genetic testing among individuals with UMMRD at a tertiary academic center. A survey evaluating interest in updated genetic testing was mailed to 98 potential participants, and an electronic health record review was completed for the 31 individuals who returned the survey. Results indicate that this population is highly interested in updated genetic testing, and their perceived impact is primarily for family members to have appropriate testing and screening options. Updated risk assessment and genetic counseling, along with a discussion of the benefits and limitations of genetic testing, is essential as the understanding of potential causes of UMMRD evolves. Updated genetic counseling may allow patients with UMMRD to better understand the interpretation of their tumor and germline testing, as well as the impact of comprehensive genetic testing for themselves and their family members

Population testing for cancer predisposing BRCA1/BRCA2 mutations

Background: Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life consequences of such an approach to family history (FH)–based testing. Methods: In a randomized controlled trial of BRCA1/2 gene-mutation testing in the Ashkenazi Jewish (AJ) population, we compared testing all participants in the population screening (PS) arm with testing those fulfilling standard FH-based clinical criteria (FH arm). Following a targeted community campaign, AJ participants older than 18 years were recruited by self-referral after pretest genetic counseling. The effects of BRCA1/2 genetic testing on acceptability, psychological impact, and quality-of-life measures were assessed by random effects regression analysis. All statistical tests were two-sided. Results: One thousand, one hundred sixty-eight AJ individuals were counseled, 1042 consented, 1034 were randomly assigned (691 women, 343 men), and 1017 were eligible for analysis. Mean age was 54.3 (SD = 14.66) years. Thirteen BRCA1/2 carriers were identified in the PS arm, nine in the FH arm. Five more carriers were detected among FH-negative FH-arm participants following study completion. There were no statistically significant differences between the FH and PS arms at seven days or three months on measures of anxiety, depression, health anxiety, distress, uncertainty, and quality-of-life. Contrast tests indicated that overall anxiety (P = .0001) and uncertainty (P = .005) associated with genetic testing decreased; positive experience scores increased (P = .0001); quality-of-life and health anxiety did not change with time. Overall, 56% of carriers did not fulfill clinical criteria for genetic testing, and the BRCA1/2 prevalence was 2.45%. Conclusion: Compared with FH-based testing, population-based genetic testing in Ashkenazi Jews doesn’t adversely affect shortterm psychological/quality-of-life outcomes and may detect 56% additional BRCA carriers

Texas Physicians\u27 Awareness and Utilization of Genetic Services

The number of disorders for which genetic testing is available has increased nearly 500% in the past 15 years. Access to the majority of genetic tests and services hinges on physicians’ ability to identify patients at risk for genetic disease and provide appropriate testing and counseling or refer to genetic specialists. Recent research demonstrates the need for referrals to genetic specialists by showing that many physicians lack skills required to perform appropriate genetic services, such as making proper risk assessments, providing genetic counseling, ordering genetic testing and interpreting results. However, little research exists on physicians’ awareness and utilization of genetic services. In this study, an electronic survey evaluating practicing physicians’ awareness of, utilization of and perceived barriers to genetic services in Texas was distributed via state physician organizations. Of the 157 participants, approximately half reported they were moderately or very aware of genetic testing and services in their area. Very few reported awareness of telemedicine services. Over two-thirds reported never or rarely referring to genetic counselors or other genetic specialists, despite 75% reporting they had noticed an increased impact of genetics on their field and 61% reporting they had discussed genetics more in their day-to-day practice in the last 5-10 years. Only 20% reported genetics was very integral to their specialty. Over three-fourths of all participants indicated interest in learning more about genetics, genetic testing and genetic services. Among the most frequently chosen barriers to genetic counselors were awareness-related barriers such as not knowing how to refer to a genetic counselor. Responses to many items varied significantly by medical specialty. The results identify a need to increase awareness of genetic services and referral logistics. Specific findings can help direct outreach efforts to educate clinicians, such as developing clinically meaningful, specialty-specific educational objectives

Implications of avoiding overlap between training and testing data sets when evaluating genomic predictions of genetic merit

The aim of this study was to evaluate and quantify the importance of avoiding overlap between training and testing subsets of data when evaluating the effectiveness of predictions of genetic merit based on genetic markers. Genomic selection holds great potential for increasing the accuracy of selection in young bulls and is likely to lead quickly to more widespread use of these young bulls with a shorter generation interval and faster genetic improvement. Practical implementations of genomic selection in dairy cattle commonly involve results of national genetic evaluations being used as the dependent variable to evaluate the predictive ability of genetic markers. Selection index theory was used to demonstrate how ignoring correlations among errors of prediction between animals in training and testing sets could result in overestimates of accuracy of genomic predictions. Correlations among errors of prediction occur when estimates of genetic merit of training animals used in prediction are taken from the same genetic evaluation as estimates for validation of animals. Selection index theory was used to show a substantial degree of error correlation when animals used for testing genomic predictions are progeny of training animals, when heritability is low, and when the number of recorded progeny for both training and testing animals is low. Even when training involves a dependent variable that is not influenced by the progeny records of testing animals (i.e., historic proofs), error correlations can still result from records of relatives of training animals contributing to both the historic proofs and the predictions of genetic merit of testing animals. A simple simulation was used to show how an error correlation could result in spurious confirmation of predictive ability that was overestimated in the training population because of ascertainment bias. Development of a method of testing genomic selection predictions that allows unbiased testing when training and testing variables are estimated breeding values from the same genetic evaluation would simplify training and testing of genomic predictions. In the meantime, a 4-step approach for separating records used for training from those used for testing after correction of fixed effects is suggested when use of progeny averages of adjusted records (e.g., daughter yield deviations) would result in inefficient use of the information available in the data.</p

European survey on knowledge and attitudes of public health professionals on public health genomics: pilot study

Background: During the past decade a debate has arisen on the possible utility of genomic science for public health purposes. Within this context, a survey is being conducted to assess attitudes of European public health (PH) professionals belonging to European Public Health Association (EUPHA) network regarding their role in the implementation of public health genomics (PHG), and their knowledge and attitudes regarding genetic testing and the delivery of genetic services. Methods: A pilot on-line survey was conducted on professionals from Sapienza University of Rome and the Vrije University of Amsterdam. The survey tool is composed of 5 sections: Personal details, Professional activity, Knowledge on genetic testing and delivery of genetic services, Attitudes on genetic testing and delivery of genetic services, Attitudes on the role of PH professionals in PHG. Results: 34 people responded to the questionnaire, mostly medical doctors (61.8%). No respondents correctly identified all evidence-based applications of genetic testing. More than one third of respondents agreed that it would be more important to invest resources in the social and environmental causes of ill health than in genetic testing. Nearly 70% thought that PHG needs to be grounded on evidence of effectiveness, a lower rate agreed ii should be grounded on cost-effectiveness. The rate of agreement with the proposed roles of PH professionals in PHG was very high. Conclusion: This pilot study showed a positive attitude but the need to improve knowledge of PH professionals on PHG. It provided useful input for the implementation of the survey to all members of the EUPHA network

Counseling Customers: Emerging Roles for Genetic Counselors in the Direct-to-Consumer Genetic Testing Market

Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing companies offer genetic counseling. There has been no examination to date of this service provision, whether it meets critics’ concerns and implications it may have for the genetic counseling profession. Considering the increasing relevance of genetics in healthcare, the complexity of genetic information provided by DTC GT, the mediating role of the internet in counseling, and potential conflicts of interest, this is a topic which deserves further attention. In this paper we offer a discourse analysis of ways in which genetic counseling is represented on DTC GT websites, blogs and other online material. This analysis identified four types of genetic counseling represented on the websites: the integrated counseling product; discretionary counseling; independent counseling; and product advice. Genetic counselors are represented as having the following roles: genetics educator; mediator; lifestyle advisor; risk interpreter; and entrepreneur. We conclude that genetic counseling as represented on DTC GT websites demonstrates shifting professional roles and forms of expertise in genetic counseling. Genetic counselors are also playing an important part in how the genetic testing market is taking shape. Our analysis offers important and timely insights into recent developments in the genetic counseling profession, which have relevance for practitioners, researchers and policy makers concerned with the evolving field of personal genomics. Keywords Genetic counseling Internet Direct-to-consumer genetic testing Discourse analysis

Clinical application of high throughput molecular screening techniques for pharmacogenomics.

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing

Genetic Testing When There is a Mix of Compulsory and Voluntary Health Insurance

Genetic insurance can deal with the negative effects of genetic testing on insurance coverage and income distribution when the insurer has access to information about test status. Hence, efficient testing is promoted. When information about prevention and test status is private, two types of social inefficiencies may occur; genetic testing may not be done when it is socially efficient and genetic testing may be done although it is socially inefficient. The first type of inefficiency is shown to be likely for consumers with compulsory insurance only, while the second type of inefficiency is more likely for those who have supplemented the compulsory insurance with substantial voluntary insurance. This second type of inefficiency is more important the less effective prevention is. It is therefore a puzzle that many countries have imposed strict regulation on the genetic information insurers have access to. A reason may be that genetic insurance is not yet a political issue, and the advantage of shared genetic information is therefore not transparent.Genetic testing insurance, private information, compulsory/voluntary mix

Testing the Children: Do Non-Genetic Health-Care Providers Differ in Their Decision to Advise Genetic Presymptomatic Testing on Minors? A Cross-Sectional Study in Five Countries in the European Union

BACKGROUND: Within Europe many guidelines exist regarding the genetic testing of minors. Predictive and presymptomatic genetic testing of minors is recommended for disorders for which medical intervention/preventive measures exist, and for which early detection improves future medical health. AIM: This study, which is part of the larger 5th EU-framework "genetic education" (GenEd) study, aimed to evaluate the self-reported responses of nongenetic health-care providers in five different EU countries (Germany, France, Sweden, the United Kingdom, and the Netherlands) when confronted with a parent requesting presymptomatic testing on a minor child for a treatable disease. METHODS: A cross-sectional study design using postal, structured scenario-based questionnaires that were sent to 8129 general practitioners (GPs) and pediatricians, between July 2004 and October 2004, addressing self-reported management of a genetic case for which early medical intervention during childhood is beneficial, involving a minor. RESULTS: Most practitioners agreed on testing the oldest child, aged 12 years (81.5% for GPs and 87.2% for pediatricians), and not testing the youngest child, aged 6 months (72.6% for GPs and 61.3% for pediatricians). After multivariate adjustment there were statistical differences between countries in recommending a genetic test for the child at the age of 8 years. Pediatricians in France (50%) and Germany (58%) would recommend a test, whereas in the United Kingdom (22%), Sweden (30%), and the Netherlands (32%) they would not. CONCLUSION: Even though presymptomatic genetic testing in minors is recommended for disorders for which medical intervention exists, EU physicians are uncertain at what age starting to do so in young children

Impact of the public/private mix of health insurance on genetic testing

Privacy of information is a central concern in the debate about genetic testing. Two types of social inefficiencies may occur when information about prevention and test status is private; genetic testing may not be done when it is socially efficient and genetic testing may be done although it is socially inefficient. The first type of inefficiency is shown to be likely for consumers with public insurance only, while the second type of inefficiency is likely for those with a mix of public/private insurance. This second type of inefficiency is shown to be more important the less effective prevention is.Health insurance; genetic testing