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Germline genetic testing has implications that extend beyond the individual patient to relatives, particularly for high-penetrance variants implicated in hereditary cancer or neurodegenerative syndromes. Many countries encourage patient-led communication to inform at-risk relatives, although the efficacy and uptake of this approach varies. Alternative scenarios envisage direct contact mediated by clinicians. The familial disclosure of sensitive genetic information is also determined by complex socio-ethnic factors. To date, no study has explored whether relatives would want to be informed of familial genetic risk and their preferences on different methods of communication in Malta. We thus used a published instrument that utilizes hypothetical scenario methodology to survey the attitudes of the Maltese population (n = 334) to receiving genetic information from family members. Two vignettes on Huntington's disease and colorectal cancer were presented. We also explored preferences towards the communication of genetic risk, confidentiality, and disclosure policies. Our preliminary results show that most respondents want to be informed of their increased risk by a family member or a clinician and would opt to receive confirmatory genetic testing. Most respondents preferred being informed of genetic risk by a close relative, but in the case of non-disclosure would want to be informed by a clinician. Most respondents expressed preference in favour of the introduction of registries, legislative change and sharing of contact details to address cases of nondisclosure. Our findings contribute further to evidence that supports, in selected hypothetical scenarios, an envisioned change in disclosure of genetic data policy by the public that is different from current practice to date., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In the genomic era, the availability of gene panel and whole genome/exome sequencing is rapidly increasing. Opportunities for providing former patients with new genetic information are also increasing over time and recontacting former patients with new information is likely to become more common. Breast cancer Refined Analysis of Sequence Tests-Risk And Penetrance (BRA-STRAP) is an Australian study of individuals who had previously undertaken BRCA1 and BRCA2 genetic testing, with no pathogenic variants detected. Using a waiver of consent, stored DNA samples were retested using a breast/ovarian cancer gene panel and clinically significant results returned to the patient (or next of kin, if deceased). This qualitative study aimed to explore patient experiences, opinions, and expectations of recontacting in the Australian hereditary cancer setting. Participants were familial cancer clinic patients (or next of kin) who were notified of a new pathogenic variant identified via BRA-STRAP. In-depth, semi-structured interviews were conducted approximately 6 weeks post-result. Interviews were transcribed verbatim and analyzed using an inductive thematic approach. Thirty participants (all female; average age = 57; range 36-84) were interviewed. Twenty-five were probands, and five were next of kin. Most women reported initial shock upon being recontacted with unexpected news, after having obtained a sense of closure related to their initial genetic testing experiences and cancer diagnosis. For most, this initial distress was short-lived, followed by a process of readjustment, meaning-making and adaptation that was facilitated by perceived clinical and personal utility of the information. Women were overall satisfied with the waiver of consent approach and recontacting process. Results are in line with previous studies suggesting that patients have positive attitudes about recontacting. Women in this study valued new genetic information gained from retesting and were satisfied with the BRA-STRAP recontact model. Practice implications to facilitate readjustment and promote psychosocial adaptation were identified., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Background: Lynch syndrome carriers ('carriers') are presented with complex, emotionally laden choices regarding management of increased genetic cancer risks. Decision aids encourage active involvement in values-based health decisions. This paper aimed to address the research question: How do Lynch syndrome carriers make sense of their chances of developing cancer, and what are the implications for providing support with decision making about genetic cancer risk management?, Methods: Adult carriers were recruited through a genetics service or involvement with Lynch Syndrome UK. Semi-structured interviews explored lived experiences of carriers' access to care with a focus on decision support. Themes were constructed using framework analysis. These were developed into a conceptual model with recommendations for codevelopment of improved information and support including a tailored decision aid to complement integrated healthcare., Results: Twenty participants included 12 women and eight men, half with a history of cancer. Six overarching themes were: (1) finding balance with Lynch; (2) living 'on higher alert'; (3) managing uncertainty: 'I've thought about it a lot'; (4) burden of responsibility: 'It's on me'; (5) access to joined-up care and support: 'There's something missing'; and (6) influence/pressure from others., Conclusions: This qualitative interview study provided in-depth insights from Lynch syndrome carriers about their lived experiences, informed by their values. Recommendations to empower carriers to make sense of genetic cancer risks and support decisions included accessible, trusted information, educated healthcare professionals, shared decision making, and joined-up integrated care pathways complemented by tailored decision aids., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Objectives: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2)., Subjects and Methods: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years. The questionnaire included questions on sociodemographics and the following measures: Hospital Anxiety and Depression Scale, Impact of Event Scale, 36-item Short-Form Health Survey, Memorial Anxiety Scale for PrCa, Cancer Worry Scale, risk perception and knowledge., Results: A total of 760 participants completed questionnaires: 207 participants with GPV in BRCA1, 265 with GPV in BRCA2 and 288 controls (non-carriers from families with a known GPV). We found no evidence of clinically concerning levels of general or cancer-specific distress or poor health-related quality of life in the cohort as a whole. Individuals in the control group had significantly less worry about PrCa compared with the carriers; however, all mean scores were low and within reported general population norms, where available. BRCA2 carriers with previously high prostate-specific antigen (PSA) levels experience a small but significant increase in PrCa anxiety (P = 0.01) and PSA-specific anxiety (P < 0.001). Cancer risk perceptions reflected information provided during genetic counselling and participants had good levels of knowledge, although this declined over time., Conclusion: This is the first study to report the longitudinal psychosocial impact of a targeted PrCa screening programme for BRCA1 and BRCA2 carriers. The results reassure that an annual PSA-based screening programme does not have an adverse impact on psychosocial health or health-related quality of life in these higher-risk individuals. These results are important as more PrCa screening is targeted to higher-risk groups., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Purpose: Germline testing in pediatric cancer presents opportunities and challenges. Understanding family perspectives, experiences, and preferences will optimize integration into routine care., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched 4 databases for studies exploring perspectives, experiences, and preferences of parents/caregivers and/or patients regarding germline testing of children with cancer. Qualitative and quantitative data were extracted, organized, and summarized by research question and themes., Results: We identified 2286 unique articles, of which 24 were included. Interest in and uptake of testing was high. Families were motivated by altruism and a desire for inheritance/causation information. Testing barriers included psychological concerns, timing of the testing approach if offered at diagnosis or in a high-risk cancer setting and privacy/discrimination. Testing experiences highlighted challenges yet also positive impacts, with results providing psychological relief and informing proactive decision making. Timing preferences varied; however, allowing time to adjust to a new diagnosis was a common theme. Most wanted to receive as many germline sequencing-related results as possible., Conclusion: Findings underscore the importance of integrating germline analyses into pediatric cancer care with flexibility and support for families facing challenges. Where possible, consent should be provided at a time that suits each family's situation with access to information aligning with their needs and preferences., Prospero: CRD42023444890., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

BRCA1/2 previvors - individuals who have a genetic mutation that increases their lifetime risk of developing breast or ovarian cancer - have unique information needs. Previvors can experience distress and uncertainty when these needs are not met, which can have negative consequences on their physical and psychological health. Previous research suggests meeting previvors' information needs is one way to combat these potential harmful effects. However, limited past research has examined previvors' perceptions of the helpfulness of information. Therefore, through surveying 101 previvors, this study explored previvors' perceptions of the (un)helpfulness of information, what (lack of) barriers previvors face to finding desired information, and the information sources they utilized. A thematic analysis revealed that previvors generally viewed information as helpful (through empowerment, coping, camaraderie, and action) but not always (evident in information overload). Previvors also reported several barriers (such as "the healthcare system in general", exclusivity, and uncertainty), while others reported a lack of resistance to finding desired information. Additionally, frequencies were calculated to find that various healthcare providers, support groups, and friends and family were common information sources. Taken together, these results offer a psychosocial model for understanding the previvor information journey, displaying how the themes are interconnected and unique for each previvor.

Individuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, and preimplantation genetic testing (PGT) in confirmed CDKN2A PV carriers and individuals with a 50% risk of the PV (at-risk carriers) using of a one-time questionnaire.A total of 537 individuals were screened for eligibility, of whom 208 of 366 (57%) confirmed carriers (56% female, median age 54 years [IQR 46-63]) and 39 of 171 (23%) at-risk carriers (59% female, median age of 26 years [IQR 22-32]) participated in the study. Primary motivations for genetic testing were to gain control over their personal and children's cancer risk, as well as increasing cancer surveillance practices. In contrast, concerns about obtaining a mortgage and life insurance were frequently cited as reasons for postponing genetic testing. Family planning decisions remained largely unaffected in both confirmed and at-risk carriers; however, the majority of confirmed carriers were still unaware of their familial or personal cancer risk when starting a family. More than 60% of the participants were unfamiliar with PGT and only a minority (19% of confirmed carriers and 10% of at-risk carriers) would be open to considering PGT as a reproductive option. This study found different attitudes toward genetic testing, family planning, and PGT among individuals affected by the CDKN2A PV. Understanding these different attitudes can help clinicians to address the complexities surrounding these issues, especially for younger individuals facing difficult decisions about the timing of genetic testing, family planning, and the potential use of assisted reproductive options., (© 2024. The Author(s).)

Observational studies have found loneliness and social isolation to mediate the relationship between childhood maltreatment and schizophrenia. Limitations with observational studies (e.g., confounding and reverse causation), however, have meant the robustness of these relationships has thus far not been explored. To address this gap, the current study utilized genomic structural equation modeling (genomic SEM) and Mendelian randomization (MR) to perform a genetic mediation analysis between childhood maltreatment, loneliness/isolation, and schizophrenia, using summary statistics from three genome-wide association studies (sample sizes 105,318-487,647). While we observed a putative effect of both childhood maltreatment (inverse variance weighted OR = 3.44 per standard deviation increase, 95% confidence interval [CI] [1.66-7.13], p < .001) and loneliness/isolation ( OR = 2.98, 95% CI [1.37-6.46], p = .006) on schizophrenia, our hypothesis that loneliness/isolation would mediate the relationship between childhood maltreatment and schizophrenia was not supported (genomic SEM indirect effect = -0.05, SE = 0.05, p = .255; MR indirect effect = 0.10, SE = 0.11, p = .369). Furthermore, reverse mediation analysis indicated that the effect may be in the opposite direction (genomic SEM indirect effect = 0.11, SE = 0.02, p < .001; MR indirect effect = 0.01, SE = 0.00, p < .001), accounting for 20.3%-28.9% of the total effect. The current results suggest that intervening in loneliness/isolation in individuals with a history of childhood maltreatment is unlikely to reduce schizophrenia risk. On the contrary, targeting loneliness/isolation in individuals with a genetic predisposition toward schizophrenia may diminish childhood maltreatment risk. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Few studies have examined the prevalence of cancer worry in the general and at-risk population. The objective of this study was to describe the prevalence of cancer worry in a sample of individuals at increased risk of developing hereditary cancer, determine differences in cancer worry by socio-demographic characteristics and assess the relationship between cancer worry and psychological distress., Methods: A cross-sectional study was designed with 895 patients. The Cancer Worry Scale (CWS), Hospital Anxiety and Depression Scale (HADS) for psychological distress and sociodemographic characteristics were examined. The multiple linear regression model was developed to explore what variables were predicted for cancer worry. To identify variables associated with higher cancer worry scores, a logistic model was fitted., Results: In the at-higher-risk sample of hereditary cancer, the mean of CWS was 10.20 (SD: 3.70). The significant predictors for cancer worry were gender, age, previous psychiatric treatment, patients affected by cancer and having children. In the sample, 38% of patients had higher scores on cancer worry, the variables associated were patients affected by cancer compared, women, widow/divorced participants, less than secondary school, patients with previous psychiatric treatment and patients less than 55 years old. Using the HADS cutoff score 29% of the sample showed significant psychological distress, more anxiety (35%) than depressive (22%) symptomatology. Psychological distress showed a higher variability (36%) on cancer worry., Conclusion: Findings highlighted distinctive profiles in socio-demographic characteristics according to the degree of cancer worry; therefore, genetic counseling should continue to be provided to address cancer worry and relieve psychological distress., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Recent research has suggested that people more readily make genetic attributions for positively valenced or desirable traits than for negatively valenced or undesirable traits-an asymmetry that may be mediated by perceptions that positive characteristics are more 'natural' than negative ones. This research sought to examine whether a similar asymmetry in genetic attributions would emerge between positive and negative health outcomes., Design: Across seven experiments, participants were randomly assigned to read a short vignette describing an individual experiencing a health problem (e.g. hypertension) or a corresponding healthy state (e.g. normal blood pressure)., Main Outcome Measures: All participants provided ratings of naturalness and genetic attributions for the outcome described in their assigned vignette., Results: For diagnoses other than addictive disorders, participants rated the presence of a diagnosis as less genetically caused than its absence; for addictive disorders, the presence of a diagnosis was rated as more genetically caused than its absence. Participants consistently rated the presence of a health problem as less natural than its absence., Conclusion: Even within a single domain of health, people ascribe differing degrees of 'naturalness' and genetic causation to positive versus negative health outcomes, which could impact their preferences for treatment and prevention strategies.

Background: Research on whole genome/exome sequencing is increasing worldwide. However, challenges are emerging in relation to receiving germline pathogenic variant results and sharing them with relatives., Objective: The aim of this study was to investigate the occurrence of and reasoning related to regret among patients with cancer who shared single-gene testing results and whole exome sequencing with family members., Methods: This was a single-center, cross-sectional study. The Decision Regret Scale was administered, and descriptive questionnaires were used with 21 patients with cancer., Results: Eight patients were classified as having no regret, 9 patients were classified as having mild regret, and 4 patients were classified as having moderate to strong regret. Reasons patients felt that sharing was the right decision included the following: to allow relatives and children to take preventive measures, the need for both parties to be aware of and ready for the hereditary transmission of cancer, and the need to be able to discuss the situation with others. On the other hand, some patients did not think it was a good decision to share the information because of the associated anxiety., Conclusions: Regret over sharing test results for pathogenic germline variants of hereditary cancers with relatives tended to be low. The main reason was that patients believed that they were able to benefit others by sharing., Implications for Practice: Healthcare professionals need to understand the postsharing perceptions and experiences of patients and support them throughout the sharing process., Competing Interests: K.Y. has received royalties from the ProGRP patent. All other authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR)., Methods: To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran's Q-test and the MR Egger intercept test., Results: The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209-2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044-1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062-2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039-1.425, P = 0.015)., Conclusions: Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs., (© 2024. The Author(s).)

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Some patients with metastatic prostate cancer carry a pathogenic germline variant (PV) in a gene, that is mainly associated with an increased risk of breast cancer in women. If they test positive for such a PV, prostate cancer patients are encouraged to disclose the genetic test result to relatives who are at risk in case the carrier status changes the relatives' medical care. Our study aimed to investigate how men who learned they carry a PV in BRCA1, BRCA2, PALB2, CHEK2 or ATM disclosed their carrier status to at-risk relatives and to assess the possible psychological burden for the carrier and their perception of the burden for relatives. In total, 23 men with metastatic prostate cancer carrying a PV completed the IRI questionnaire about family communication; 14 also participated in a semi-structured interview. Patients felt highly confident in discussing the genetic test result with relatives. The diagnosis of prostate cancer was experienced as a burden, whereas being informed about genetic testing results did in most cases not add to this burden. Two patients encountered negative experiences with family communication, as they considered the genetic test result to be more urgent than their relatives. This mixed-methods study shows that metastatic prostate cancer patients with a PV in genes mainly associated with increased risk of breast cancer feel well-equipped to communicate about this predisposition in their families. Carriers felt motivated to disclose their genetic test result to relatives. Most of them indicated that the disclosure was not experienced as a psychological burden., (© 2024. The Author(s).)

Purpose: This study aims to shed light on the rather neglected area of research of psychological distress in women facing genetic counselling in Turkey, where few institutions providing such counselling exist., Methods: 105 breast cancer patients presenting for genetic testing completed a sociodemographic and clinical questionnaire as well as validated structured questionnaires including the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI-S/T) and the Health Motivation Sub-dimension of Champion's Health Belief Model Scale., Results: 69.5% of the participants had lost a family member from cancer; 80% said the term "cancer" elicited negative thoughts (e.g., death, fear, and incurable disease). 62.9% and 37.1% attributed cancer to stress or sorrow, and genetic susceptibility, respectively. There was a negative association between health motivation and BDI scores (r:-0.433, p < 0.001). Married individuals had higher BDI and STAI-S scores (p = 0.001, p = 0.01 respectively), as well as lower STAI-T scores (p = 0.006). BDI, STAI-S and STAI-T scores were higher in those refusing genetic testing (p < 0.001, p < 0.001, p = 0.003 respectively) and those with metastases (p = 0.03, p = 0.01, p = 0.03 respectively). Furthermore, individuals with low health motivation were more likely to exhibit high BDI scores (p < 0.001) and low STAI-T scores (p = 0.02)., Conclusion: Common perceptions and beliefs about cancer and genetic testing during genetic counselling were found to have a negative impact on distress in high-risk women with breast cancer. The negative relationship between psychological distress and health motivation may reduce patients' compliance with genetic counselling recommendations. A comprehensive psychological evaluation should be considered as an important part of genetic counselling., (© 2024. The Author(s).)

Background & Aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes., Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3 months postintervention., Results: A total of 424 families were randomized, including 601 participants (n = 296 Arm 1; n = 305 Arm 2), 90% of whom completed genetic testing (Arm 1 [87%]; Arm 2 [93%], P = .014). Arm 1 participants were significantly less likely to complete genetic testing compared with Arm 2 participants (adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). Among participants who completed patient-reported psychological outcomes questionnaires (Arm 1 [n = 194]; Arm 2 [n = 206]), the intervention did not affect mean anxiety, depression, or cancer worry scores., Conclusions: Remote genetic education and testing can be a successful and complementary option for delivering genetics care. (Clinicaltrials.gov, number NCT03762590)., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Understanding service user preferences is key to effective health care decision making and efficient resource allocation. It is of particular importance in the management of high-risk patients in whom predictive genetic testing can alter health outcomes., Purpose: This review aims to identify the relative importance and willingness to pay for attributes of genetic testing in hereditary cancer syndromes., Data Sources: Searches were conducted in Medline, Embase, PsycINFO, HMIC, Web of Science, and EconLit using discrete choice experiment (DCE) terms combined with terms related to hereditary cancer syndromes, malignancy synonyms, and genetic testing., Study Selection: Following independent screening by 3 reviewers, 7 studies fulfilled the inclusion criteria, being a DCE investigating patient or public preferences related to predictive genetic testing for hereditary cancer syndromes., Data Extraction: Extracted data included study and respondent characteristics, DCE attributes and levels, methods of data analysis and interpretation, and key study findings., Data Synthesis: Studies covered colorectal, breast, and ovarian cancer syndromes. Results were summarized in a narrative synthesis and the quality assessed using the Lancsar and Louviere framework., Limitations: This review focuses only on DCE design and testing for hereditary cancer syndromes rather than other complex diseases. Challenges also arose from heterogeneity in attributes and levels., Conclusions: Test effectiveness and detection rates were consistently important to respondents and thus should be prioritized by policy makers. Accuracy, cost, and wait time, while also important, showed variation between studies, although overall reduction in cost may improve uptake. Patients and the public would be willing to pay for improved detection and clinician over insurance provider involvement. Future studies should seek to contextualize findings by considering the impact of sociodemographic characteristics, health system coverage, and insurance policies on preferences., Highlights: Test effectiveness and detection rates are consistently important to respondents in genetic testing for hereditary cancer syndromes.Reducing the cost of genetic testing for hereditary cancer syndromes may improve uptake.Individuals are most willing to pay for a test that improves detection rates, identifies multiple cancers, and for which results are shared with a doctor rather than with an insurance provider., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, and/or publication of this article.

Introduction: In the USA, patients who undergo genetic testing for hereditary cancer risk are responsible for informing relatives about their genetic test results, but many relatives never find out they might be at risk. A health system-mediated relative notification program might help fill this gap, but questions remain about the acceptability of this approach., Methods: We analyzed qualitative data from a single-arm, nonrandomized, mixed-methods study to understand how patients and families experienced a new health system-mediated relative notification program. We invited all study participants to participate in semi-structured telephone interviews at 6-8 weeks after return of genetic test results. We used a template analysis approach to thematically analyze interview transcripts., Results: We interviewed 32 participants, including 17 probands and 15 relatives. Relatives reported positive experiences with the notification program, noting they felt in control of decisions and appreciated genetic counselor involvement in communicating the proband's test results. Benefits of direct contact included reduced burden for probands, increased family discussions about health, and notification of relatives who otherwise would not have learned results. No participants reported adverse effects from the program., Conclusion: Overall, the relative notification program was acceptable to participants and supported probands in reaching at-risk relatives who otherwise might not have been notified. These findings could inform the implementation of future genetic risk family notification programs with the potential to improve uptake of cascade testing and advance cancer prevention and early detection efforts., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Although the prevalence of a pathogenic variant in the BRCA1 and BRCA2 genes is about 1:400 (0.25%) in the general population, the prevalence is as high as 1:40 (2.5%) among the Ashkenazi Jewish population. Despite cost-effective preventive measures for mutation carriers, Orthodox Jews constitute a cultural and religious group that requires different approaches to BRCA1 and BRCA2 genetic testing relative to other groups. This study analyzed a dialog of key stakeholders and community members to explore factors that influence decision-making about BRCA1 and BRCA2 genetic testing in the New York Orthodox Jewish community., Methods: Qualitative research methods, based on Grounded Theory and Narrative Research, were utilized to analyze the narrative data collected from 49 key stakeholders and community members. A content analysis was conducted to identify themes; inter-rater reliability was 71%., Results: Facilitators of genetic testing were a desire for preventive interventions and education, while barriers to genetic testing included negative emotions, feared impact on family/romantic relationships, cost, and stigma. Views differed on the role of religious leaders and healthcare professionals in medical decision-making. Education, health, and community were discussed as influential factors, and concerns were expressed about disclosure, implementation, and information needs., Conclusion: This study elicited the opinions of Orthodox Jewish women (decision-makers) and key stakeholders (influencers) who play critical roles in the medical decision-making process. The findings have broad implications for engaging community stakeholders within faith-based or culturally distinct groups to ensure better utilization of healthcare services for cancer screening and prevention designed to improve population health., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

We sought to explore individuals' motivations for using their direct-to-consumer genetic testing data to generate polygenic risk scores (PRSs) using a not-for-profit third-party tool, and to assess understanding of, and reaction to their results. Using a cross-sectional design, users of Impute.me who had already accessed PRS results were invited to complete an online questionnaire asking about demographics, motivations for seeking PRSs, understanding and interpretation of PRSs, and two validated scales regarding reactions to results-the Impact of Event Scale Revised (IES-R) and the Feelings About genomiC Testing Results (FACToR). Independent samples T-tests and ANOVA were used to explore associations between the variables. 227 individuals participated in the study. The most frequently reported motivation was general curiosity (98.2%). Only 25.6% of participants correctly answered all questions assessing understanding/interpretation of PRSs. Over half of participants (60.8%) experienced a negative reaction (upset, anxious, and/or sad on FACToR scale) after receiving their PRSs and 5.3% scored over the threshold for potential post-traumatic stress disorder on the IES-R. Lower understanding about PRS was associated with experiencing a negative psychological reaction (P values <0.001). Higher quality pre-test information, particularly to improve understanding, and manage expectations for PRS may be useful in limiting negative psychological reactions., (© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.)

While prior studies have largely focused on family communication of diagnostic single-gene test results or specific types of cancer testing results, far less work has investigated family communication of cancer-related genetic results that include multi-gene panels, a broad array of cancer types/stages, and participants without family history of cancer. The study we report here examined individuals' anticipated barriers and benefits to sharing genetic information with family members. An 80+ gene panel was performed on participants recruited from Mayo Clinic, diagnosed with different cancer types, who did not have a family history suggestive of an inherited risk. Participants completed a 49-item survey before receiving genetic test results. Family variant testing was provided to family members at no cost, allowing factors influencing intent to share to be examined in the absence of financial burdens. In all, 1721 of 2984 individuals who received genetic testing completed the survey (57.7% completion rate). Participants' intent to share with parents, siblings, and children was inversely related to the number of anticipated barriers to sharing and directly related to the number of anticipated benefits to sharing. Of those participants who did not intend to share with parents, siblings, and adult children, 64.8%, 30.3%, and 67.6% reported that there were no barriers, while 17.1%, 24.5%, and 40.2.% reported there were no benefits. Findings indicate that barriers to sharing genetic information with family members vary across family member types, and an inability to identify at least one benefit of sharing with family members is a predictor of intent not to share., (© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.)

Importance: Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families., Objective: To assess the psychosocial effect of nGS on families from the BabySeq Project, a randomized clinical trial evaluating the effect of nGS on the clinical care of newborns from well-baby nurseries and intensive care units., Design, Setting, and Participants: In this randomized clinical trial conducted from May 14, 2015, to May 21, 2019, at well-baby nurseries and intensive care units at 3 Boston, Massachusetts, area hospitals, 519 parents of 325 infants completed surveys at enrollment, immediately after disclosure of nGS results, and 3 and 10 months after results disclosure. Statistical analysis was performed on a per-protocol basis from January 16, 2019, to December 1, 2019., Intervention: Newborns were randomized to receive either standard newborn screening and a family history report (control group) or the same plus an nGS report of childhood-onset conditions and highly actionable adult-onset conditions (nGS group)., Main Outcomes and Measures: Mean responses were compared between groups and, within the nGS group, between parents of children who received a monogenic disease risk finding and those who did not in 3 domains of psychosocial impact: parent-child relationship (Mother-to-Infant Bonding Scale), parents' relationship (Kansas Marital Satisfaction Scale), and parents' psychological distress (Edinburgh Postnatal Depression Scale anxiety subscale)., Results: A total of 519 parents (275 women [53.0%]; mean [SD] age, 35.1 [4.5] years) were included in this study. Although mean scores differed for some outcomes at singular time points, generalized estimating equations models did not show meaningful differences in parent-child relationship (between-group difference in adjusted mean [SE] Mother-to-Infant Bonding Scale scores: postdisclosure, 0.04 [0.15]; 3 months, -0.18 [0.18]; 10 months, -0.07 [0.20]; joint P = .57) or parents' psychological distress (between-group ratio of adjusted mean [SE] Edinburgh Postnatal Depression Scale anxiety subscale scores: postdisclosure, 1.04 [0.08]; 3 months, 1.07 [0.11]; joint P = .80) response patterns between study groups over time for any measures analyzed in these 2 domains. Response patterns on one parents' relationship measure differed between groups over time (between-group difference in adjusted mean [SE] Kansas Marital Satisfaction Scale scores: postdisclosure, -0.19 [0.07]; 3 months, -0.04 [0.07]; and 10 months, -0.01 [0.08]; joint P = .02), but the effect decreased over time and no difference was observed on the conflict measure responses over time. We found no evidence of persistent negative psychosocial effect in any domain., Conclusions and Relevance: In this randomized clinical trial of nGS, there was no persistent negative psychosocial effect on families among those who received nGS nor among those who received a monogenic disease risk finding for their infant., Trial Registration: ClinicalTrials.gov Identifier: NCT02422511.

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none.

Background: Carriers of deleterious mutations in breast cancer predisposition genes are presented with critical choices regarding cancer risk management. Risk-reduction mastectomy is a major preventative strategy in this population. Understanding the decision-making process for prophylactic mastectomy is essential in patient-centered care for high-risk carriers and patients with breast cancer. We sought to provide insight into influential factors underlying preventative surgery decisions among individuals with high breast cancer risk., Materials and Methods: We conducted a retrospective chart review of pathogenic carriers of high-risk breast cancer genes who presented to the Moffitt GeneHome clinic between March 2017 and June 2020. Associations between preventative mastectomy choice and influence variables were analyzed via unadjusted and adjusted logistic regression models., Results: Of 258 high-risk mutation carriers, 104 (40.3%) underwent risk-reduction mastectomy. A significantly higher proportion of mastectomy patients reported prior history of breast cancer (68.9% vs. 16.5%; P < .001) and history of other risk-reduction or noncancer-related surgeries (61.7% vs. 25.8%; P < .001). Significant predictors affecting surgery decision included previous breast cancer history (adjusted odds ratio [aOR], 10.48; 95% confidence interval [CI], 5.59-19.63; P < .0001), other risk-reduction or noncancer-related surgical history (aOR, 4.65; 95% CI, 2.28-9.47; P < .0001), and age at presentation to the genetics clinic (< 35 years old: aOR, 2.77; 95% CI, 1.04-7.4; P = .042; 35-55 years old: aOR, 2.48; 95% CI, 1.19-5.18; P = .016)., Conclusions: Preventive mastectomy decisions are highly personal and complex. In our sample, we observed prior history or concurrent breast cancer, history of other risk-reduction surgery or noncancer-related surgery, and younger age at presentation to the GeneHome clinic to be predictive of mastectomy uptake., (Copyright © 2021. Published by Elsevier Inc.)

Objective: We examined parental diabetes monitoring behaviors in a cohort of children at increased genetic risk for type 1 diabetes. We hypothesized that being informed of a positive islet autoantibody (IA) would increase monitoring behaviors., Research Design and Methods: The Environmental Determinants of Diabetes in the Young (TEDDY) study follows 8676 children with high-risk human leucocyte antigen-DQ genotypes from birth to age 15, including general population (GP) children and those with a first-degree relative (FDR) with diabetes. Data on parental monitoring behaviors were solicited yearly. Serum samples were tested for IA and parents were informed of child results. We examined parental monitoring behaviors during the first 7 years of TEDDY., Results: In IA- children, the most common monitoring behavior was participating in TEDDY study tasks; up to 49.8% and 44.2% of mothers and fathers, respectively, reported this. Among FDRs, 7%-10% reported watching for diabetes symptoms and 7%-9% reported monitoring the child's glucose, for mothers and fathers, respectively. After IA+ notification, all monitoring behaviors significantly increased in GP parents; only glucose monitoring increased in FDR parents and these behaviors continued for up to 4 years. FDR status, accurate diabetes risk perception, and anxiety were associated with glucose monitoring in IA+ and IA- cohorts., Conclusions: Many parents view TEDDY participation as a way to monitor for type 1 diabetes, a benefit of enrollment in a longitudinal study with no prevention offered. IA+ notification increases short- and long-term monitoring behaviors. For IA- and IA+ children, FDR parents engage in glucose monitoring, even when not instructed to do so., (© 2021 John Wiley & Sons Ltd.)

The introduction of psychiatric genetic evidence in court proceedings to terminate parental rights raises concerns that such information will result in misconceived assumptions about the child's mental health trajectory and unjust rulings on termination of parental rights. We conducted an online vignette-based survey with a nationally representative sample of adults from the general public ( n = 300 respondents) to assess their views on how evidence about a child's psychiatric genetic makeup may affect key decisions in termination proceedings. Our findings indicate that genetic evidence increased the child's labeling as having a psychiatric disorder, regardless of the presence of symptoms, treatment recommendations, evaluation of prescription medication, and beliefs in treatment efficacy. Genetic evidence alone did not affect whether participants would terminate parental rights, but participants who thought that the child did not have a psychiatric disorder were more likely to terminate in the presence of genetic test results. We conclude that psychiatric genetic evidence in termination proceedings may have unintended consequences, and that measures should be taken to ensure that it does not unfairly affect outcomes., (© 2021 American Academy of Psychiatry and the Law.)

Purpose: Since the U.S. Food and Drug Administration approved sales of genetic tests for late-onset Alzheimer's disease (LOAD) risk, a heated debate has arisen over whether these tests should indeed be offered online and direct-to-consumer (DTC). As this debate progresses, it is important to understand the ethical perspectives and motivations of young people, who are a key target group for DTC services., Methods: Thirty-one grandchildren of people with LOAD, aged 16-26, were interviewed about their moral attitudes and motivations with regards to DTC genetic testing for LOAD., Results: Even though most participants claimed that people should have the right to access these services, they also expressed concerns about potential distress in response to learning about risk, particularly for minors. About a third were interested in testing, primarily to gain self-knowledge regarding one's health; however, face-to-face services were vastly preferred over the online option., Conclusion: While DTC genetic companies often market their services as a "fun consumer product", DTC testing for LOAD was largely understood as a serious health screening procedure and a vulnerable moment in the lives of young people in Alzheimer's families. This points to the importance of appropriate standards of information and support to young people pre- and post-testing., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts., (Published by Elsevier Masson SAS.)

Background: When a woman is diagnosed with hereditary breast or ovarian cancer, family members may be at high risk of cancers associated with BRCA1/2 gene mutation and benefit from disclosure of the genetic test result. This duty of informing relatives may be distressing, or relatives may not be properly informed., Objective: To qualitatively describe breast cancer patients' experiences communicating genetic risk of cancer to their relatives., Methods: Probands with BRCA1/2 gene mutations were recruited from an oncology institute in Istanbul, Turkey, and interviewed by telephone. Qualitative content analysis was conducted to derive central elements of the 30 women's experiences communicating genetic risk to their relatives., Results: Six themes were identified: response to genetic test results, reason for communication, feelings about communication, reflection after communication, results of communication, and needs., Conclusion: Women with cancer found to have BRCA1/2 gene mutations tended to share their genetic test results within the family. The main motives for sharing test results were the desire to encourage relatives to get tested and moral and ethical convictions. Women needed explicit information regarding cancer risk and risk-reducing strategies to act upon., Implications for Practice: The women's feelings and reflections about the communication process were varied and suggest that personalized genetic risk communication interventions may better support women with BRCA1/2 gene mutations during and after communication with relatives. Long-term follow-up of those women is essential because of the need for informed decision on risk-reducing strategies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

The low uptake of presymptomatic testing in Huntington disease prompted us to question family members on how they handle the transmission of information regarding genetic risk. We hypothesised that in 2019, parents would inform their at-risk children about their genetic risk more and at a younger age than in 2000, given the availability of prenatal diagnosis, French legislation changes since 2011, and recent therapeutic advances. We made a questionnaire available about the transmission of genetic information within families with Huntington disease in 2000 and 2019. We obtained 443 questionnaires (295 in 2019 and 148 in 2000). Participants were mainly at-risk for Huntington disease (n = 113), affected (n = 85), and spouses (n = 154). In 2019, participants had a higher mean education level (p < 0.01) and a mean age of 44.1 ± 15.1 years (vs 48.1 ± 11.4 years in 2000, p < 0.01). They had been informed about the risk of being a carrier at around 30 years of age (29.0 ± 14.2 in 2019 vs 32.2 ± 13.8 in 2000, p = 0.09). However, they would inform at an earlier age (≤18 years, 67% vs 59%, p = 0.16). Information on transmission risk had been given primarily by parents (45% vs 30%, p = 0.06). In addition, genetic testing for relatives unaware of their status was recommended more frequently in 2019 (46% vs 32%, p < 0.001). Respondents in 2019 recommended genetic testing more often but overall attitudes towards information and testing have not changed significantly over the 19-year time period since the questionnaire was first delivered even despite recent clinical trials potential disease modifying therapies.

Background: Understanding multiple components of risk perceptions is important because perceived risk predicts engagement in prevention behaviors., Purpose: To examine how multiple components of risk perceptions (perceived magnitude of and worry about risk, prioritization of the management of one's risk) changed following genetic counseling with or without test reporting, and to examine which of these components prospectively predicted improvements in sun-protection behavior 1 year later., Methods: A prospective, nonrandomized study design was used. Participants were 114 unaffected members of melanoma-prone families who (i) underwent genetic testing for a CDKN2A/p16 mutation (n = 69) or (ii) were at comparably elevated risk based on family history and underwent genetic counseling but not testing (no-test controls, n = 45). Participants reported risk perception components and sun-protection behavior at baseline, immediately following counseling, and 1 month and 1 year after counseling., Results: Factor analysis indicated three risk components. Carriers reported increased perceived magnitude and priority of risk, but not cancer worry. No-test controls showed no changes in any risk perception. Among noncarriers, priority of risk remained high at all assessments, whereas magnitude of risk and cancer worry decreased. Of the three risk components, greater priority of risk uniquely predicted improved self-reported sun protection 1 year post-counseling., Conclusions: Priority of risk (i) seems to be a component of risk perceptions distinguishable from magnitude of risk and cancer worry, (ii) may be an important predictor of daily prevention behavior, and (iii) remained elevated 1 year following genetic counseling only for participants who received a positive melanoma genetic test result., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Relatively little is known about the possible effects of personalized genetic risk information on smoking, the leading preventable cause of morbidity and mortality. We examined the acceptability and potential behavior change associated with a personalized genetically informed risk tool ( RiskProfile ) among current smokers. Current smokers ( n = 108) were enrolled in a pre-post study with three visits. At visit 1, participants completed a baseline assessment and genetic testing via 23andMe. Participants' raw genetic data ( CHRNA5 variants) and smoking heaviness were used to create a tailored RiskProfile tool that communicated personalized risks of smoking-related diseases and evidence-based recommendations to promote cessation. Participants received their personalized RiskProfile intervention at visit 2, approximately 6 weeks later. Visit 3 involved a telephone-based follow-up assessment 30 days after intervention. Of enrolled participants, 83% were retained across the three visits. Immediately following intervention, acceptability of RiskProfile was high (M = 4.4; SD = 0.6 on scale of 1 to 5); at 30-day follow-up, 89% of participants demonstrated accurate recall of key intervention messages. In the full analysis set of this single-arm trial, cigarettes smoked per day decreased from intervention to 30-day follow-up [11.3 vs. 9.8; difference = 1.5; 95% confidence interval (0.6-2.4); P = 0.001]. A personalized genetically informed risk tool was found to be highly acceptable and associated with a reduction in smoking, although the absence of a control group must be addressed in future research. This study demonstrates proof of concept for translating key basic science findings into a genetically informed risk tool that was used to promote progress toward smoking cessation. Prevention Relevance: This study demonstrates that personal genetic information can be incorporated into a risk feedback tool that was highly acceptable to current smokers and associated with reductions in smoking. These findings may pave the way for effectiveness and implementation research on genetically-informed behavior change interventions to enhance cancer prevention efforts., (©2020 American Association for Cancer Research.)

Purpose: Genetic research, via the mainstream media, presents the public with novel, profound findings almost on a daily basis. However, it is not clear how much laypeople understand these presentations and how they integrate such new findings into their knowledge base. Genetic knowledge (GK), existing causal beliefs, and genetic essentialist tendencies (GET) have been implicated in such processes; the current study assesses the relationships between these elements and how brief presentations of media releases of scientific findings about genetics are consumed and affect the readers., Methods: An Australian national survey of GK, GET, and existing causal beliefs about health phenomena (heart disease and obesity) was conducted. Participants were also exposed to news headlines that offered genetic and non-genetic partial explanations of the same health phenomena and reported their evaluations of these headlines, as well as the effects of the headlines on their personal understanding of the health phenomena., Results: GK was negatively-associated with GET. Whereas GK did not directly predict the evaluation and effects of the genetic headlines, GET did. GK predicted the effects of the headlines indirectly via GET and via GET and existing causal beliefs., Conclusion: GET seem to predict unwarranted effects of exposure to news headlines about genetic science, whereas GK seems to indirectly mitigate the same unwarranted effects., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Couples at increased risk of having offspring with a specific genetic disorder who want to avoid having an affected child have several reproductive options including prenatal diagnosis (PND) and preimplantation genetic testing (PGT). In the future, non-invasive prenatal diagnosis (NIPD), germline gene editing (GGE) and somatic gene editing (SGE) might become available. This study explores if, and how, availability of new genetic technologies, including NIPD, GGE, SGE, would change reproductive decision-making of high-risk couples. In 2018, semi-structured interviews were conducted with 25 genetically at-risk couples. Couples previously had received genetic counselling for PND and PGT, and in most cases opted for (one of) these techniques, at one Dutch Clinical Genetics Center between 2013 and 2017. Considerations participants mentioned regarding the hypothetical use of NIPD, GGE and SGE, seem similar to considerations regarding PND and PGT and are reflected in underlying concepts. These include safety and burden for mother and child, and moral considerations. Couples generally favoured NIPD over PND as this would be safe and enables earlier diagnosis. Increased opportunities of having a 'healthy' embryo and less embryo disposal were considerations in favour of GGE. Some regarded GGE as unsafe and feared slippery slope scenarios. Couples were least favourable towards SGE compared to choosing for a genetic reproductive technology, because of the perceived burden for the affected offspring. With the possibly growing number of technological options, understanding high risk couples' perspectives can assist in navigating the reproductive decision-making process. Counsellors should be prepared to counsel on more and complex reproductive options.

Purpose of Review: Eating behaviours are hypothesised to be the behavioural expression of genetic risk of obesity. In this review, we summarise findings from behavioural genetic research on the association between genetic risk for obesity and validated psychometrics measures of eating behaviours in children and adults (published in the past 10 years)., Recent Findings: Twin studies have produced some evidence for a shared genetic aetiology underlying body mass index and eating behaviours. Studies using measured genetic susceptibility to obesity have suggested that increased genetic liability for obesity is associated with variation in obesogenic eating behaviours such as emotional and uncontrolled eating. More research on this topic is needed. Especially longitudinal studies using genetically sensitive designs to investigate the direction of genetic pathways between genetic liability of eating behaviours to weight and vice versa, as well as the potential subsequent link to eating disorders.

Purpose : While a large body of evidence has shown that the administration of the measles-mumps-rubella (MMR) vaccine is not associated with an increased risk of autism spectrum disorder (ASD), a hesitant attitude towards childhood vaccination is still present among the public. In this study, we aim to investigate the mothers' perceptions of the cause of their child's ASD in order to increase our understanding of vaccine hesitancy. Methods : This study draws on the analysis of 18 semi-structured interviews of mothers of children with ASD on the causes of autism. Results : The interview material was content-analysed. The main themes were 1) childhood vaccines; 2) genetics; 3) specific conditions of the mother or the newborn at the moment of delivery; 4) environmental factors such as the mother's lifestyle or her diet. The link between vaccines and autism was prevalent. About one third of the mothers reported that their child's ASD was a consequence of a combination of two or more factors, i.e., childhood vaccines and specific conditions of the newborn or the mother at the moment of delivery. Conclusion : This study provides preliminary insights into recurring sets of beliefs concerning the causes of ASD among the mothers of affected children.

Objective: To synthesize research findings about reproductive decision making among women who are BRCA positive., Data Sources: PubMed and CINAHL., Study Selection: Articles published in English between 2000 and June 28, 2020, about the reproductive decision making of women with a confirmed BRCA1 or BRCA2 mutation., Data Extraction: We extracted data about participants, study design, analysis, follow-up, and results. We used the modified Downs and Black checklist and Kennelly's qualitative data analysis to rate studies for quality and applicability by using., Data Synthesis: We included five of 257 screened articles in our synthesis. The total sample size of the five studies was 1,468 women. The most prevalent factors related to reproductive decision making were the impending decisions regarding childbearing and family choices, including decisions about biological children, preventive surgery, preimplantation genetic diagnosis, and prenatal diagnosis to prevent further transmission of a BRCA mutation, and family planning., Conclusion: A lack of knowledge exists about the reproductive decision-making processes of women who are BRCA positive. A better understanding of this process would provide nurses and other clinicians with the knowledge needed to support these women through their reproductive life choices., (Copyright © 2020 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

The general public is increasingly aware of the role of genes in causing depression. Recent studies have begun uncovering unintended negative consequences of learning about a person's genetic susceptibility to disorders. Because people tend to believe that genes determine one's identity, having genes related to a disorder can be misinterpreted as equivalent to having the disorder. Consequently, learning that a person is genetically predisposed to depression can make people misremember mild depression as more severe. Participants across three experiments read a target vignette about a character displaying mild depressive symptoms, while descriptions of the character's genetic susceptibility to depression were experimentally manipulated. Participants then read a foil vignette describing a character with more severe depressive symptoms. Afterwards, participants who had learned that the target character was genetically predisposed to depression were comparatively more likely to misremember the target symptoms as being severe, when in fact they were mild. This pattern of results was obtained among both laypeople (Experiments 1 and 2) and practicing master's-level, but not doctoral-level, mental health clinicians (Experiment 3). Given that depression is diagnosed primarily based on a person's memory of depressive symptoms, the current findings suggest that genetic information about depression may lead to over-diagnosis of depression., Competing Interests: The authors have declared that no competing interests exist.

Objective: Leventhal's common sense model of self-regulation highlights how specific beliefs about illness influence psychological outcomes. Little is known on how such beliefs relate to BRCA1/2 adjustment. Furthermore, beliefs about one's self-concept may be relevant to genetic conditions and may relate to psychological wellbeing., Methods: One-hundred and eighteen female BRCA1/2 carriers from an Irish University Hospital completed questionnaires for this cross-sectional study. Outcomes measured were state anxiety and physical and mental health-related quality of life (HRQOL). Explanatory variables included sociodemographics, health anxiety, illness perceptions, coping and self-concept. Hierarchical multiple regression analyses were conducted., Results: Then, 44% of participants had clinically significant state anxiety and 12% had clinically significant health anxiety. Vulnerability, stigma, mastery and health anxiety explained 42% of the variance in state anxiety. Previous mental health difficulty, vulnerability, stigma, mastery and health anxiety explained 40% of the variance in mental HRQOL. Dysfunctional coping strategies were strongly related to the physical functioning aspect of quality of life., Conclusion: BRCA-specific beliefs related to self and health anxiety are important factors to consider in the adjustment to BRCA1/2 confirmation., (© 2020 John Wiley & Sons Ltd.)

Background: Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk., Methods: In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10 -4 p=5 × 10 -5 p=5 × 10 -6 p=5 × 10 -7 , and p=5 × 10 -8 ) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2-4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor., Findings: The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10 -5 ) showed the strongest association with gastric cancer risk (p=7·56 × 10 -10 ). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (p trend <0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio [HR] 1·54 [95% CI 1·22-1·94], p=2·67 × 10 -4 ) and a high genetic risk (2·08 [1·61-2·69], p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (p trend <0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 [1·46-2·83], p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 [0·29-0·99], p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62-1·56)., Interpretation: Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer., Funding: National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The authors aimed to clarify the sources of parent-child transmission for suicide attempt and death by suicide., Methods: Three sources of parent-child resemblance (genes plus rearing, genes only, and rearing only) were examined in parents and offspring from four family types from Swedish national samples: intact nuclear families, families with a not-lived-with biological father, families with a stepfather, and adoptees and their biological and adoptive parents. Parent-child resemblance was assessed primarily by tetrachoric correlation., Results: For suicide attempt to suicide attempt transmission, best-estimate tetrachoric correlations for genes plus rearing, genes only, and rearing only were 0.23 (95% CI=0.23, 0.24), 0.13 (95% CI=0.11, 0.15), and 0.14 (95% CI=0.11, 0.16), respectively. Suicide attempt was more strongly transmitted to male offspring compared with female offspring. Parental psychiatric disorders accounted for 40% of the genetic transmission but had no impact on rearing effects. For suicide death to suicide death transmission, best estimates of tetrachoric correlations for genes plus rearing, genes only, and rearing only were 0.16 (95% CI=0.15, 0.18), 0.07 (95% CI=0.02, 0.12), and -0.05 (95% CI=-0.17, 0.07), respectively. Although the suicide attempt-suicide death genetic correlation was high (0.84), the hypothesis that they reflect behaviors only differing in severity on the same continuum of genetic liability could be rejected., Conclusions: The transmission of suicide attempt across generations is moderately strong and arises equally from genetic and rearing effects. Parental psychiatric illness explains almost half of the genetic transmission of suicide attempt but none of the rearing effect. Suicide death is modestly transmitted across generations, probably via genetic effects, although rearing may play a role. While suicide attempt and suicide death share a substantial proportion of their hereditary risk, they do not, from a genetic perspective, simply reflect milder and more severe forms of the same diathesis.

Aims: There is evidence that individuals with psychosis adopt inefficient coping styles. Moreover, it has been hypothesized that inefficient coping styles might serve as trait-dependent characteristics of psychosis. Therefore, we aimed to explore coping styles and their clinical correlates at various stages of psychosis., Methods: We recruited 37 individuals at familial high risk of psychosis (FHR-P), 42 individuals with first-episode psychosis (FEP), 28 acutely relapsed schizophrenia (SCZ-AR) subjects and 40 healthy controls. Coping strategies were assessed using the Coping Inventory for Stressful Situations., Results: Individuals with FEP were less likely to use task-focused coping, while SCZ-AR subjects preferred using distraction when compared to controls. Both groups of participants did not differ significantly in terms of using specific coping styles. No significant differences in the use of various coping strategies between FHR-P individuals and controls were found. Higher odds of using emotion-focused coping and distraction were associated with more severe depressive symptoms in individuals with psychosis. Moreover, higher frequency of using distraction was associated with worse functioning in individuals with psychosis. However, this association appeared to be insignificant after adjustment for multiple testing., Conclusions: Coping styles are similar in FEP and SCZ-AR subjects. However, decreased use of task-focused coping is more specific for FEP individuals while a preference of distraction might be more typical for SCZ-AR individuals. The use of various coping styles is similar in FHR-P individuals and controls. Preference of distraction and emotion-focused coping might be related to more severe depressive symptoms and poor functioning in individuals with psychosis., (© 2019 John Wiley & Sons Australia, Ltd.)

Objective: Adolescent and young adult (AYA) cancer patients have distinct medical and psychosocial needs and fertility is a key concern. Early age of onset is a risk factor for hereditary cancer and AYAs are more likely to experience reduced fertility. This has implications for future family building decisions and fertility preservation (FP) and genetic testing/counseling (GT/GC) education., Methods: Patients diagnosed with cancer between the ages of 18 and 39 and health care providers (HCPs) who treat AYA cancer patients were recruited from a single institution. Qualitative interviews explored AYA patients' and HCPs' concerns regarding their experiences discussing genetics and FP., Results: The majority of patients (n = 17) were female (59%), and the majority of HCPs (n = 18) were male (67%). Overall, participants had differing perceptions of FP and GT/GC-related information provided during the clinical visit. Patients indicated initiating the conversation about FP and did not recall HCPs discussing GT/GC with them. HCPs indicated patients were often overwhelmed with too much information and comprehension of this discussion is limited. HCPs also felt patients' emotions/beliefs determined their information-seeking behavior specific to FP and GT/GC. Participants felt educational materials should be developed and delivered in a video format depicting a patient-provider interaction or patient testimonial., Conclusion: AYA patients are often overwhelmed by a cancer diagnosis; the complexity/volume of information regarding FP and GT/GC may hinder understanding and decision-making about family building. Educational materials that help patients understand what questions to ask HCPs about FP and GT/GC should be developed to improve knowledge, psychosocial well-being, and future family building decisions.

There is growing impetus to include measures of personal utility, the nonmedical value of information, in addition to clinical utility in health technology assessment (HTA) of genomic tests such as genomic sequencing (GS). However, personal utility and clinical utility are challenging to define and measure. This study aimed to explore what drives patients' preferences for hypothetically learning medically actionable and non-medically actionable secondary findings (SF), capturing clinical and personal utility; this may inform development of measures to evaluate patient outcomes following return of SF. Semi-structured interviews were conducted with adults with a personal or family cancer history participating in a trial of a decision aid for selection of SF from genomic sequencing (GS) ( www.GenomicsADvISER.com ). Interviews were analyzed thematically using constant comparison. Preserving health-related and non-health-related quality of life was an overarching motivator for both learning and not learning SF. Some participants perceived that learning SF would help them "have a good quality of life" through informing actions to maintain physical health or leading to psychological benefits such as emotional preparation for disease. Other participants preferred not to learn SF because results "could ruin your quality of life," such as by causing negative psychological impacts. Measuring health-related and non-health-related quality of life may capture outcomes related to clinical and personal utility of GS and SF, which have previously been challenging to measure. Without appropriate measures, generating and synthesizing evidence to evaluate genomic technologies such as GS will continue to be a challenge, and will undervalue potential benefits of GS and SF.

The field of cardiovascular genetic counseling has evolved dramatically in recent years largely to manage the unique psychological needs of the inherited cardiovascular disease patient population. For many, there can be difficulty in coming to terms with a diagnosis, whether it be adjusting to lifestyle recommendations such as exclusion from competitive sports or living with a small but remarkable risk of sudden cardiac death. For those considered at risk of life-threatening ventricular arrhythmias, the decision to have an implantable cardioverter defibrillator can be difficult. Living with the device, especially for those who are young and those who receive multiple shocks, can precipitate psychological distress and poor adaptation to the device. Family members who experience a sudden cardiac death of a young relative have a significant risk of poor psychological outcomes. The roles of the cardiac genetic counselor in facilitating patients' adaptation to their diagnoses and management and recognizing when additional support from a clinical psychologist is needed are key to ensuring families receive the best possible care., (Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.)

This study aims to enrich our understanding of factors influencing medically indicated at-risk individuals' decisions to take genetic tests (or not) in the context of cancer treatment and prevention. While previous studies have explored this topic in communities in Europe and the United States, we know relatively little about the situation in Asia. In this study, we conducted in-depth interviews with 24 women who underwent genetic testing for hereditary breast and ovarian cancer syndromes in Singapore. Grounded theory with thematic analysis was applied. Six encouraging and three discouraging factors are identified in the analysis. The six encouraging factors are: desire to create awareness for self and family; perceived benefits for self and family; strong family history of cancer; presence of family support; medical professional recommendation and adequate amount of time to consider undertaking the test. The three discouraging factors are: high costs of tests; perceived lack of ability to cope with test results; and insufficient information about genetic testing. Taken together, the findings in this study add to the current literature by providing empirical evidence regarding the importance of holding family included pre-test counselling and providing adequate time for patients to decide to undergo genetic testing for hereditary cancer syndromes., (© 2020 John Wiley & Sons Ltd.)

Objective: Genetic testing for hereditary breast and ovarian cancer (HBOC) due to pathogenic variants in BRCA1 or BRCA2 is why most women present to familial cancer centers. Despite being assessed as low risk for HBOC, many women proceed with genetic testing. This study explored the genetic testing experiences of unaffected women at low risk of HBOC to clarify what motivates these women to have testing, and what are the implications of the results., Methods: A qualitative approach was taken. Participants included women who had genetic testing for HBOC from 2016-2018 at the Parkville Familial Cancer Centre in Melbourne, Australia. In-depth, semi-structured interviews were conducted, and thematic analysis was undertaken on transcripts; transcripts were coded, codes were organized into a hierarchical system of categories/subcategories, and key themes were identified., Results: Analysis of 19 transcripts identified five themes: family underpinned all motivators for HBOC genetic testing; health professionals were influential throughout the process; participants were planning for a positive result; results influenced screening-anxiety and frequency; and negative results gave participants relief in many different ways. The three participants with positive results reported feeling shocked at the results and empowered giving this information to family members., Conclusions: Women at low HBOC risk may be motivated to seek genetic testing, and access to this is increasingly offered through non-genetic health professionals. Professionals can support clients through genetic testing by recognizing familial experiences, providing accurate information, addressing risk perceptions, and understanding cancer anxiety felt by many women., (© 2020 John Wiley & Sons, Ltd.)

Genetic testing decision-making for cancer predisposition is inherently complex. Understanding the mechanisms and influencing factors of the decision-making process is essential for genetic counselling and has not yet been investigated in Switzerland. This study's aim is thus to provide a theory about the individual's decision-making process regarding genetic testing for cancer predispositions in order to provide medical geneticists and genetic counsellors with insights into the needs and expectations of counsellees. We interviewed at-risk individuals who underwent genetic counselling in a clinical setting in Switzerland, using a grounded theory approach. Based on the interview data, we propose that a control-fate continuum, which is part of the individuals' life philosophy, importantly influences the decision-making process. Those in need for control decide differently compared with those leaving their future to fate. Several psychosocial factors influence the position on the control-fate continuum: "looking for certainty"; "anticipating consequences"; "being socially influenced"; "simplifying risks"; and "deciding intuitively vs reflectively". The control-fate continuum theory gives insights into the possible reasons behind decision-making regarding genetic testing for cancer predispositions. It includes both acceptors and decliners of genetic testing. Our theory helps healthcare professionals offering genetic counselling to anticipate problems within at-risk families and adapting their services to people's needs.

Purpose: To understand the process of discovery and decision making for adults with the CDH1 marker for hereditary diffuse gastric cancer and inherited breast cancer., Participants & Setting: Purposeful sampling included 20 participants., Methodologic Approach: Grounded theory with constant comparison was used., Findings: The decision-making process of Paving the Way addresses the challenges for individuals diagnosed with the CDH1 marker. The theory explains the process of learning the risk, discerning testing, choosing iterative individual interventions, and adjusting postoperatively while normalizing to live longer., Implications for Nursing: The process explains and describes the nine factors for decision making and predicts the timing for nursing interventions for genetic testing and pre- and postoperative assessment and planning.

Schizophrenia is a severe psychiatric disorder with considerable morbidity and mortality. Although the past two decades have seen limited improvement in the treatment of schizophrenia, research into the genetic causes of this condition has made important advances that offer new insights into the aetiology of schizophrenia. This Review summarizes the evidence for a polygenic architecture of schizophrenia that involves a large number of risk alleles across the whole range of population frequencies. These genetic risk loci implicate biological processes related to neurodevelopment, neuronal excitability, synaptic function and the immune system in the pathogenesis of schizophrenia. Mathematical models also suggest a substantial overlap between schizophrenia and psychiatric, behavioural and cognitive traits, a situation that has implications for understanding its clinical epidemiology, psychiatric nosology and pathobiology. Looking ahead, further genetic discoveries are expected to lead to clinically relevant predictive approaches for identifying high-risk individuals, improved diagnostic accuracy, increased yield from drug development programmes and improved stratification strategies to address the heterogeneous disease course and treatment responses observed among affected patients.