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BACKGROUND Genetic testing has become an integrated part of the health care for patients with breast or ovarian cancer, and the increasing demand of genetic testing is accompanied by an increasing need of easy access to reliable genetic information for patients. We therefore developed an app (named Rosa), a virtual assistant able to perform human-like digital conversations about genetic BRCA-testing, using chatbot technology. OBJECTIVE Before implementing this new information service in daily clinical practice, we wanted to explore two aspects of chatbot use: 1) The perceived utility and trust in chatbot technology among healthy patients at risk of hereditary cancer, and 2) How interaction with a chatbot regarding sensitive information about hereditary cancer, influences the patients. METHODS A total of 175 healthy individuals at risk of hereditary breast and ovarian cancer, were invited to test the chatbot Rosa before and after genetic counseling. Among 61 participants that consented for individual interview, a selected subgroup of 16 subjects shared their experience through in-depth interviews over video. To secure a varied sample, the participants were recruited from all cancer genetic clinics in Norway and the selection was based on age, gender, and risk of having a BRCA pathogenic variant. RESULTS The overall finding was that the chatbot was very welcomed by the participants. They appreciated the 24/7 availability, and that they could have access wherever they were. The fact that Rosa was created by health care professionals made them feel safe that they received medically correct information. It was referred to as an alternative to Google, only better, since it provided specific and reliable answers to their questions. All participants denied increased worry after reading about genetic testing and hereditary breast and ovarian cancer in Rosa. CONCLUSIONS This study shows that chatbot use in clinical genetic practice contributes to uniform information for our patients, regardless of residence and access to specialized healthcare personnel, without adding discomfort or worry. The availability of quality assured information, tailored to the specific situation the patient is facing, has had a reassuring effect on the participants. This indicates that a chatbot can be a well-suited companion to genetic counseling, however we found no evidence supporting that Rosa could replace genetic counseling.

Contains fulltext : 202775.pdf (Publisher’s version ) (Open Access) BACKGROUND: Genetic testing is increasing in patients newly diagnosed with cancer. This study investigated the levels, course and predictors of cancer-related distress, defined as intrusion and avoidance, in women undergoing BRCA1/2 testing without pretest genetic counseling shortly after a diagnosis of breast or ovarian cancer. MATERIAL AND METHODS: Unselected for family history or age, 259 women with breast cancer and 50 women with ovarian cancer, underwent BRCA1/2 testing shortly after diagnosis. Cancer-related distress was measured with the Impact of Event Scale before and after genetic testing. In order to identify predictors of distress, the subscale scores were regressed on baseline predictor variables including sociodemographic and medical variables, perceived social support, and decisional conflict regarding genetic testing. RESULTS: The mean levels of intrusion and avoidance were in the moderate range both before and after genetic testing with a statistically significant decline during follow-up. Younger age, shorter time since diagnosis, lower levels of social support, and a diagnosis of ovarian cancer predicted higher levels of both intrusion and avoidance. In addition, higher levels of decisional conflict and living with a partner predicted higher levels of intrusion. CONCLUSIONS: Women having genetic testing shortly after a diagnosis of breast or ovarian cancer had a moderate mean level of cancer-related distress, which decreased with time. Health personnel offering genetic testing to newly diagnosed women with breast or ovarian cancer should be aware of the potential predictors for increased cancer-related distress identified in this study: younger age, less perceived social support, higher levels of decisional conflict regarding genetic testing, and living with a partner.

Objective: We aimed at developing a pilot version of an app (Rosa) that can perform digital conversations with breast or ovarian cancer patients about genetic BRCA testing, using chatbot technology, to identify best practices for future patient-focused chatbots. Methods: We chose a commercial chatbot platform and participatory methodology with a team of patient representatives, IT engineers, genetic counselors and clinical geneticists, within a nationwide collaboration. An iterative approach ensured extensive user and formal usability testing during the development process. Results: The development phase lasted for two years until the pilot version was completed in December 2019. The iteration steps disclosed major challenges in the artificial intelligence (AI)-based matching of user provided questions with predefined information in the database, leading initially to high level of fallback answers. We therefore developed strategies to reduce potential language ambiguities (e.g. BRCA1 vs BRCA2) and overcome dialogue confusion. The first prototype contained a database with 500 predefined questions and 67 corresponding predefined answers, while the final version included 2257 predefined questions and 144 predefined answers. Despite the limited AI functionality of the chatbot, the testing revealed that the users liked the layout and found the chatbot trustworthy and reader friendly. Conclusions: Building a health chatbot is challenging, expensive and time consuming with today’s technology. The users had a positive attitude to the chatbot, and would use it in a real life setting, if given to them by health care personnel. Practice implications: We here present a framework for future health chatbot initiatives. The participatory methodology in combination with an iterative approach ensured that the patient perspective was incorporated at every level of the development process. We strongly recommend this approach in patient-centered health innovations. publishedVersion

Rare sequence variants in the non-coding part of the BRCA genes are often reported as variants of uncertain significance (VUS), which leave patients and doctors in a challenging position. The aim of this study was to determine the pathogenicity of the BRCA1 c.5407-25T>A variant found in 20 families from Norway, France and United States with suspected hereditary breast and ovarian cancer. This was done by combining clinical and family information with allele frequency data, and assessment of the variant’s effect on mRNA splicing. Mean age at breast (n = 12) and ovarian (n = 11) cancer diagnosis in female carriers was 49.9 and 60.4 years, respectively. The mean Manchester score in the 20 families was 16.4. The allele frequency of BRCA1 c.5407-25T>A was 1/64,566 in non-Finnish Europeans (gnomAD database v2.1.1). We found the variant in 1/400 anonymous Norwegian blood donors and 0/784 in-house exomes. Sequencing of patient-derived cDNA from blood, normal breast and ovarian tissue showed that BRCA1 c.5407-25T>A leads to skipping of exon 23, resulting in frameshift and protein truncation: p.(Gly1803GlnfsTer11). Western blot analysis of transiently expressed BRCA1 proteins in HeLa cells showed a reduced amount of the truncated protein compared with wild type. Noteworthily, we found that a small amount of full-length transcript was also generated from the c.5407-25T>A allele, potentially explaining the intermediate cancer burden in families carrying this variant. In summary, our results show that BRCA1 c.5407-25T>A leads to partial skipping of exon 23, and could represent a likely pathogenic variant with reduced penetrance.

Rare sequence variants in the non-coding part of the BRCA genes are often reported as variants of uncertain significance (VUS), which leave patients and doctors in a challenging position. The aim of this study was to determine the pathogenicity of the BRCA1 c.5407-25T>A variant found in 20 families from Norway, France and United States with suspected hereditary breast and ovarian cancer. This was done by combining clinical and family information with allele frequency data, and assessment of the variant’s effect on mRNA splicing. Mean age at breast (n = 12) and ovarian (n = 11) cancer diagnosis in female carriers was 49.9 and 60.4 years, respectively. The mean Manchester score in the 20 families was 16.4. The allele frequency of BRCA1 c.5407-25T>A was 1/64,566 in non-Finnish Europeans (gnomAD database v2.1.1). We found the variant in 1/400 anonymous Norwegian blood donors and 0/784 in-house exomes. Sequencing of patient-derived cDNA from blood, normal breast and ovarian tissue showed that BRCA1 c.5407-25T>A leads to skipping of exon 23, resulting in frameshift and protein truncation: p.(Gly1803GlnfsTer11). Western blot analysis of transiently expressed BRCA1 proteins in HeLa cells showed a reduced amount of the truncated protein compared with wild type. Noteworthily, we found that a small amount of full-length transcript was also generated from the c.5407-25T>A allele, potentially explaining the intermediate cancer burden in families carrying this variant. In summary, our results show that BRCA1 c.5407-25T>A leads to partial skipping of exon 23, and could represent a likely pathogenic variant with reduced penetrance.

EMBO Reports (2019) e47812 New breeding techniques, in particular gene editing technologies such as CRISPR, have great potential to transform agri‐ and aquaculture. However, realising this potential depends in large part on the regulation of genetically engineered products. Given the rapid technological progress in molecular biology, and the widely diverging interests of stakeholders, there is an urgent need for novel approaches regarding the governance of genetically engineered crops and animals along with a restart of the public dialogue. Importantly, regulation should stimulate technological development while simultaneously maintaining governmental oversight and control; however, the EU's current regulatory regime for genetically modified organisms (GMOs) is not necessarily conducive for stimulating development of new products. We therefore propose a differentiated regulatory framework that would considerably lower the regulatory hurdles for certain uses of genetic engineering, and stimulate innovation and development to the benefit of society, while allowing flexibility in terms of risk assessment. We further call upon relevant authorities and governments to advance policy development and facilitate a goal‐oriented and inclusive public dialogue. The aim is to harness the potential of gene technologies in a safe, beneficial, sustainable and ethically justifiable manner while maintaining public trust. ### The Current Situation In July 2018, after years of regulatory uncertainty in the EU, the European Court of Justice decided that all gene‐edited organisms are subject to the approval requirements that currently apply to the deliberate release of GMO under EU Directive 2001/18/EC [1]. The court's decision has been criticised by many European scientists [2], [3], [4], [5], who assert that it jeopardises the future of agriculture and food‐related research and development in the EU. In particular, many critics highlight that the current regulatory landscape will prevent the use of gene editing to rapidly develop novel agricultural products to deal …

Genetic testing for hereditary breast and ovarian cancer is increasingly being offered in newly diagnosed breast and ovarian cancer patients. This genetic information may influence treatment decisions. However, there are some concerns that genetic testing offered in an already vulnerable situation might be an extra burden to these women. The aim of this study was to explore the experiences of women who had been offered and accepted genetic testing when newly diagnosed with breast or ovarian cancer. Four semi-structured focus-group interviews were conducted with 17 women recruited from a Norwegian multicenter study. The material was condensed, and conventional qualitative analysis was used to identify patterns in the participants' descriptions. Three core themes were identified: 1) being "beside oneself" 2) altruism and ethical dilemmas 3) the need for support and counselling to assist the decision process. The present study indicates that women who are offered genetic testing when newly diagnosed with breast or ovarian cancer want a consultation with a health professional. Personalized support and counselling might empower women to improve their ability to manage and comprehend this overwhelming situation, and find meaning in this experience.

Background Women carrying BRCA-mutations are facing significant challenges, including decision making regarding surveillance and risk-reducing surgery. They often report that they are left alone with these important decisions. In order to enhance the genetic counselling session we organized a group-based patient education (GPE) course for women with BRCA-mutations. The study aims were to characterize women attending a group-based patient education (GPE) course for hereditary breast and ovarian cancer, consider the usefulness of the course, evaluate symptoms of anxiety and depression among the participants, and finally investigate whether their levels of anxiety and depression changed from before to after the course session. Methods A prospective study was conducted. Two weeks before (T1) and 2 weeks after (T2) attending the GPE-course the participants received questionnaires by mail. We collected information on demographic- and medical variables, anxiety and depression using Hospital Anxiety and Depression Scale (HADS), self-efficacy using The Bergen Genetic Counseling Self-Efficacy scale (BGCSES) and coping style using the Threatening Medical Situations Inventory (TMSI). A total of N = 100 (77% response rate) women participated at baseline and 75 (58% response rate) also completed post-course assessment. Results The mean level of anxiety symptoms was elevated among participants but decreased significantly during follow-up. Lower anxiety symptom levels were associated with “longer time since disclosure of gene test result”, “higher levels of self-efficacy” and having experienced “loss of a close relative due to breast or ovarian cancer”. Lower depression symptom levels were associated with “higher levels of education” and “loss of a close relative due to breast or ovarian cancer”. Conclusion The women in this study seemed to benefit from the GPE course. Women newly diagnosed with a BRCA mutation who reported lower levels of self-efficacy and lower levels of education were more vulnerable. These women need special attention.

Contains fulltext : 172006.pdf (Publisher’s version ) (Open Access) Germline BRCA1/2 testing of breast and ovarian cancer patients is growing rapidly as the result affects both treatment and cancer prevention in patients and relatives. Through the DNA-BONus study we offered BRCA1/2 testing and familial risk assessment to all new patients with breast (N=893) or ovarian (N=122) cancer diagnosed between September 2012 and April 2015, irrespective of family history or age, and without prior face-to-face genetic counselling. BRCA1/2 testing was accepted by 405 (45.4%) and 83 (68.0%) of the patients with breast or ovarian cancer, respectively. A pathogenic BRCA1/2 variant was found in 7 (1.7%) of the breast cancer patients and 19 (22.3%) of the ovarian cancer patients. In retrospect, all BRCA1/2 mutation carriers appeared to fulfill current criteria for BRCA1/2 testing. Hospital Anxiety and Depression Scale (HADS) scores showed that the mean levels of anxiety and depression were comparable to those reported for breast and gynecological cancer patients in general, with a significant drop in anxiety symptoms during a 6-month follow-up period, during which the test result was forwarded to the patients. These results show that BRCA1/2 testing is well accepted in newly diagnosed breast and ovarian cancer patients. Current test criteria based on age and family history are sufficient to identify most BRCA1/2 mutation carriers among breast cancer patients. We recommend germline BRCA1/2 testing in all patients with epithelial ovarian cancer because of the high prevalence of pathogenic BRCA1/2 variants.

Genetic counseling for hereditary cancer is expected to involve a growing number of individuals in the near future since an increasing number of genetic tests are offered. This study was designed to identify psychosocial variables predicting distress after genetic investigation and genetic counseling (GC) in order to develop new counseling strategies.A prospective multi-site study was undertaken on 214 patients undergoing GC for hereditary cancer to explore the relationships between socio-demographic variables, medical variables, social support, self-efficacy, physical functioning, satisfaction with GC, the level of worry after GC, results of genetic testing, and the course and outcomes of distress. Distress was measured with the Impact of Event Scale, which includes subscales of intrusion and avoidance. Patients completed questionnaires mailed to them before and after GC.The mean level of intrusion and avoidance was moderate, even though one quarter of participants reported a severe level of intrusion at baseline. Subjects with a low level of self-efficacy at baseline and high level of worry immediately after GC seemed to be vulnerable to both intrusion and avoidance. Lower level of intrusion was also associated with having a first-degree relative with cancer, while a lower avoidance level was associated with a higher level of education, having cancer, more social support, and higher satisfaction with GC.In this study, subjects who had lower level of self-efficacy at baseline and a high level of worry immediately after GC seemed to be vulnerable to both intrusion and avoidance in this study.

Background Long QT syndrome is an inherited heart-rhythm disorder characterized by an increased risk of ventricular tachycardia and sudden death. Genetic testing is available. Material and methods The article is based on an anonymous family with a history of long QT syndrome, the authors experience with this patient group and a Pubmed search for literature from the period 1957 - 2007. Results An 8-year-old boy suffers syncope at a sports event, and this leads to genetic counseling and molecular genetic testing of his first-and second-degree relatives. Knowledge about genetic risk of sudden death in a family can trigger genetic testing and health preventive treatment of children, but can also have substantial psychosocial and ethical consequences for the family and for the health-care personnel involved. Interpretation Living with a genetic risk can be very emotionally challenging for the individuals and families, and "The Norwegian Act of Biotechnology in Human Medicine, etc" that regulates clinical genetic activities is extensive. An important question is whether the current Act allows communication of genetic information to persons other than the patient.

Objectives The main aims of the study were to investigate changes in anxiety and depression over time in subjects attending genetic counseling (GC) for hereditary cancer, and secondly, to identify psychological, social, and medical variables associated with the course and outcome of anxiety and depression. Methods Of 275 eligible individuals, 221 consented to participate, 214 returned the baseline questionnaire, and were included in a prospective multi-center study. Questionnaires were mailed to the subjects before and after the GC. Results The mean values for anxiety and depression were quite low at all assessments. Mixed linear analyzes revealed that both anxiety and depression declined over time. Higher age, GC-related self-efficacy, and social support were associated with lower levels of anxiety. More social support, satisfaction with GC, self-rated physical function, and GC-related self-efficacy were associated with lower levels of depression. The effects of social support on both anxiety and depression had a significant interaction with time. Conclusion The results support the buffer theory, which proposes that social support acts as a buffer, protecting people from the potentially pathogenic influence of stressful life events, such as GC. Practice implications Subjects with less social support and less GC-related self-efficacy seem to be more vulnerable to anxiety and depression and should be offered extra attention by counselors.

In this multi center study, genetic counseling for hereditary cancer was evaluated by assessing patients' worry, perceived risk of developing cancer and satisfaction with genetic counseling. An overall aim was to identify characteristics of vulnerable patients in order to customize genetic counseling. In addition, agreement between patients' and counselors' scores was measured. A total of 275 Norwegian patients were consecutively recruited, and 213 completed questionnaires before and after genetic counseling. Patients' perceived risk decreased after the genetic counseling session. There was incongruence between risk perception expressed as a percentage and in words. Patients were significantly less worried after counseling. Higher levels of worry were predicted by low instrumental satisfaction with counseling, high degree of perceived risk of developing cancer and younger age. In conclusion, counselors met the patients' psychological needs to a satisfactory degree during counseling. However, patients did not fully understand their risk of developing cancer.

The aim of this multicenter study was to explore associations between psychosocial factors (general self-efficacy, perceived availability of social support, cancer-related distress) and health-related quality of life, among individuals at risk for hereditary cancer. One-hundred and twenty one participants with a family history of breast-cancer or colorectal cancer answered a questionnaire 2-4 weeks prior to genetic counseling. The two dimensions of the health-related quality of life measure, mental and physical health were both used as outcome variables. Multiple regression (linear) analyses revealed that increasing degrees of cancer-related distress was related to decreasing degrees of mental health whereas increasing degrees of self-efficacy and social support were related to increasing degrees of this outcome variable. Self-efficacy, self-esteem support and tangible aid seemed to moderate the relationship between cancer-related distress and mental health. These results suggest that self-efficacy and certain resources of social support buffer the negative association between cancer-related distress and mental health, and might be suitable for interventional efforts. Implications for genetic counseling practice are discussed.

PURPOSE: The aim of this paper was to investigate whether cancer genetic counseling could be considered as a stressful event and associated with more anxiety and/or depression compared to other cancer-related events for instance attending mammography screening or receiving a cancer diagnosis.METHODS: A total of 4911 individuals from three Scandinavian countries were included in the study. Data was collected from individuals who had attended either cancer genetic counseling (self-referred and physician-referred) or routine mammography screening, were recalled for a second mammograpy due to a suspicious mammogram, had received a cancer diagnosis or had received medical follow-up after a breast cancer-surgery. Data from the genetic counseling group was also compared to normative data. Participants filled in the Hospital Anxiety and Depression Scale twice: prior to a potentially stressful event and 14 days after the event.RESULTS: Pre-counseling cancer genetic counselees reported significant lower level of anxiety compared to the cancer-related group, but higher levels of anxiety compared to the general population. Furthermore, the level of depression observed within the genetic counseling group was lower compared to other participants. Post-event there was no significant difference in anxiety levels between the cancer genetic counselees and all other groups; however, the level of depression reported in the self-referred group was significantly lower than observed in all other groups. Notably, the level of anxiety and depression had decreased significantly from pre-to post-events within the genetic counseling group. In the cancer-related group only the level of anxiety had decreased significantly post-event.CONCLUSION: Individuals who attend cancer genetic counseling do not suffer more anxiety or depression compared to all other cancer-related groups. However, some counselees might need additional sessions and extended support. Thus, identifying extremely worried individuals who need more support, and allocating further resources to their care, seems to be more sufficient.

Since Long QT syndrome and Hypertrophic cardiomyopathy are inherited cardiac disorders that may cause syncope, palpitations, serious arrhythmias, and sudden cardiac death, at-risk individuals may experience heart-focused anxiety. In a prospective multi-site study, 126 Norwegian patients attending genetic counseling were followed 1 year with multiple administration of questionnaires, including the Cardiac Anxiety Questionnaire, measuring three distinct symptoms of heart-focused anxiety- avoidance, attention, and fear—in mixed linear analyses. Overall, at 1-year follow-up, patients with clinical diagnosis as compared to patients at genetic risk had significantly higher scores of avoidance (p

Background The possibilities in the molecular genetics of long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) has made family screening, with diagnostic and predictive genetic testing part of the health care offer in genetic counselling of inherited arrhythmias, potentially affecting the subjective health among these individuals. The study compared health status among patients at risk of arrhythmia because of family history or clinical diagnosis of LQTS and HCM with reference health status scores of the general population. Methods In the period 2005-2007, 127 patients (mean age 45 years, 53.5% women), with a family history of arrhythmia (n = 95) or a clinical diagnosis of LQTS (n = 12) or HCM (n = 19) referred for genetic counselling at the medical genetic departments in Norway filled in a questionnaire (Short Form Health Survey SF-36) measuring health status on eight domains. The patient SF-36 scores were compared to expected scores of the general population by t-test, and the relationship between the socio-demographic variables, clinical status, and SF-36 domains were analysed by multiple linear regression. Results The total sample reported significant lower SF-36 score as compared to the general population scores for the domain of general health (mean difference -7.3 ( Conclusions Having a genetic risk of arrhythmia affects general health significantly. In addition, patients with a clinical diagnosis of HCM demonstrate a significantly poorer health in both physical and mental domains.

Long QT syndrome is an inherited heart-rhythm disorder characterized by an increased risk of ventricular tachycardia and sudden death. Genetic testing is available.The article is based on an anonymous family with a history of long QT syndrome, the authors experience with this patient group and a Pubmed search for literature from the period 1957 - 2007.An 8-year-old boy suffers syncope at a sports event, and this leads to genetic counseling and molecular genetic testing of his first-and second-degree relatives. Knowledge about genetic risk of sudden death in a family can trigger genetic testing and health preventive treatment of children, but can also have substantial psychosocial and ethical consequences for the family and for the health-care personnel involved.Living with a genetic risk can be very emotionally challenging for the individuals and families, and "The Norwegian Act of Biotechnology in Human Medicine, etc" that regulates clinical genetic activities is extensive. An important question is whether the current Act allows communication of genetic information to persons other than the patient.

Long QT syndrome (LQTS) is a congenital disorder associated with increased risk of sudden cardiac death; LQTS patients and their families are offered diagnostic or predictive genetic testing. The purpose of this qualitative study was to investigate the psychosocial aspects of living with LQTS, to identify LQTS patients’ daily life challenges and coping strategies, and to describe their experiences with healthcare services. In-depth interviews were conducted with seven individuals who had been tested for long QT genetic mutation. Four of these participants had an implantable cardiac defibrillator (ICD). The participants reported that early and gradually acquired knowledge of the syndrome was an advantage. They also reported experiencing worries and limitations in daily life, but their main concern was for their children or grandchildren. Healthcare providers’ minimal knowledge of LQTS resulted in uncertainty, misinformation, and even wrong advice regarding treatment. The results suggest that regional centers, with the appropriate expertise, should investigate and counsel LQTS patients and their families.

This study examines the association between Sense of Coherence and anxiety and depression amongst patients at risk of hereditary cancer receiving genetic counseling. When writing this article, 144 patients referred for genetic counseling due to a suspicion of hereditary cancer in the family were recruited for this multicentered longitudinal study on the psychosocial aspects of genetic counseling in Norway. A total of 96 (66%) patients responded to the follow-up survey distributed 6 months after genetic counseling. This survey included the Sense of Coherence-29 Scale, Impact of Event Scale, and Hospital Anxiety and Depression Scale. Multiple regression analyses were applied. Our results show association between cancer-related distress and symptoms of anxiety and depression. Sense of Coherence is significantly associated with both anxiety and depression. The hypothesis of Sense of Coherence buffering cancer-related distress and the possible impact of these findings for genetic counseling are discussed.