Cancer Susceptibility Genetic Testing in a High-Risk Cohort of Urban Ashkenazi Jewish Individuals

Prior to 2013, genetic testing for Ashkenazi Jewish (AJ) individuals primarily consisted of the three-site BRCA1/BRCA2 AJ panel, full sequencing of BRCA1/2, or the Lynch syndrome mismatch repair genes. Multigene panel testing became more widely available in 2013, but limited data are available regarding the impact of multigene panel testing for AJ individuals. Here, we report the frequency of cancer susceptibility gene mutations in a cohort of 427 AJ individuals seen in the Cancer Risk Clinic at The University of Chicago. We found that 29% of affected and 37% of unaffected individuals carried a pathogenic mutation (32% of overall cohort), primarily known familial mutations in BRCA1/2. A minority of mutations were identified in non-BRCA1/2 genes and consisted mainly of AJ founder mutations in CHEK2, APC, and the mismatch repair genes. A panel of AJ founder mutations would have identified the majority (94%) of mutations in clinically actionable genes in both affected and unaffected patients. Based on recent cost-effectiveness studies, offering all AJ individuals a founder mutation panel may be a cost-effective cancer prevention strategy.     

Impact of Genetic Counseling in Women with a Family History of Breast Cancer in Italy

As the impact of breast cancer (BC) risk assessment in asymptomatic women with a family history of BC had never been explored in Italy, we performed a study on a retrospective series of women who had undergone BC risk assessment. To this aim, a semi-structured telephone interview was administered to 82 women. Most participants considered the information received as clear (96.2 %) and helpful (76.8 %). Thirty-eight (46.3 %) stated that their perceived risk of BC had changed after the counseling: for 40.2 % it had decreased, for 6.1 % increased; however, women highly overestimating their risk at the baseline (≥4-fold) failed to show improvements in risk perception accuracy. Sixty-six women (80.5 %) stated they had followed the recommended surveillance, while 19.5 % had not, mainly due to difficulties in arranging examinations. Most women (89.0 %) had shared the information with their relatives, with 57.3 % reporting other family members had undertaken the recommended surveillance. BC risk assessment was associated with high rates of satisfaction and had a favorable impact on risk perception in a subgroup of women. The impact on surveillance adhesion extended to relatives. Organized programs for identification and surveillance may help identify a larger fraction of at-risk women and overcome the reported difficulties in arranging surveillance.     

Efficacy of the Health Belief Model for Predicting Intention to Pursue Genetic Testing for Colorectal Cancer

This study examined the Health Belief Model’s efficacy to predict intention to undergo genetic testing for the Colorectal Carcinoma (CRC) gene within a rural/frontier setting. Survey data were collected on 558 Southwest Montanan residents. Regression analysis revealed that perceived benefits, including affordability and satisfying curiosity, were the strongest indicators of intention to undergo genetic testing for CRC. Select consumer barriers and cues to action variables were also found to be significant predictors. Collectively the model explained approximately 36% of the variance. These preliminary findings have implications for genetic counselors, health practitioners and health care providers concerned with genetic counseling and addressing the public health issue of CRC.     

The Use of Family History Questionnaires: An Examination of Genetic Risk Estimates and Genetic Testing Eligibility in the Non-responder Population

The use of mailed family history questionnaires (FHQs) has previously been established to be an effective method for obtaining family history information for the triage of patients for genetic counseling and genetic testing of hereditary breast and ovarian cancer syndrome; yet only 53% of patients complete their FHQ within 6 months from the date of mailing (Armel et al. Journal of Genetic Counseling, 18(4):366–378, 2009). Although literature exists evaluating why women may not attend genetic counseling, no data are currently available examining genetic risk or genetic testing eligibility in the population of patients not returning their FHQ (non-responders). Concern exists that if non-responders are not followed-up for the purpose of triage for genetic counseling, individuals at high-risk for a hereditary cancer syndrome may be missed. This article explores the demographics of the non-responder population to assess genetic risk estimates for mutations in the BRCA1 and BRCA2 genes and genetic testing eligibility as compared to a responder population of patients who completed a mailed FHQ. A total of 430 pedigrees were obtained, 215 from non-responders and 215 from responders. Results of this study indicate that 69% of non-responders were either unreachable by telephone (42%), declined an appointment (19%), or were previously seen in another center for a genetic counseling visit (8%). Additionally, results indicate that non-responders are less likely to be eligible for genetic testing (40%) as compared to responders (57%) (p = 0.0004). Together these data shed light on a population of patients for which limited information exists and suggest that we question how and to what extent clinics should pursue non-responders, particularly in light of global reductions in health care funding.     

Living with Long QT Syndrome: A Qualitative Study of Coping with Increased Risk of Sudden Cardiac Death

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.     

Amyotrophic Lateral Sclerosis in a Patient with a Family History of Huntington Disease: Genetic Counseling Challenges

Amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) are generally considered to be distinct and easily differentiated neurologic conditions. However, there are case reports of the co-occurrence of ALS with HD. We present a 57-year-old male with a clinical diagnosis of sporadic ALS in the context of a family history of HD. This case adds to the limited literature regarding individuals with a family history of HD who present with features of ALS. There were several genetic counseling challenges in counseling this patient including the diagnostic consideration of two fatal conditions, complex risk information, the personal and familial implications, and the patient’s inability to communicate verbally or through writing due to disease progression. DNA banking effectively preserved the right of our patient and his wife not to learn his HD genetic status during a stressful time of disease progression while providing the option for family members to learn this information in the future if desired. We present lessons learned and considerations for other clinical genetics professionals who are presented with similar challenging issues.     

Investigation of the Use of a Family Health History Application in Genetic Counseling

The paper-based pedigree is the current standard for family health history (FHH) documentation in genetic counseling. Several tools for electronic capture of family health data have been developed to improve re-use and accessibility, data quality and standardization, ease of updating, and integration with electronic medical records. One such tool, the tablet-based Proband application, provides a flexible approach to data capture in dynamic and diverse clinical settings. This study compared Proband FHH collection to paper-based methods and investigated the usability of Proband in a clinical setting. After one use by 23 genetic counselors and students, Proband had 91% accuracy with a FHH audio scenario, which was significantly less (p?<?0.001) than paper’s 96% accuracy. These differences were attributed to incorrect or missing ages of grandparents (p?<?0.001) and great-aunts/uncles (p?=?0.012) and missing documentation of consanguinity (p?<?0.001). Possible explanations for these differences include greater experience with paper FHH documentation and pre-populated prompts for consanguinity on the paper template used. Proband’s perceived usability increased with use, with individual System Usability Scores increasing between first and last use (p?=?0.033). We conclude that tools for dynamic, provider-driven FHH documentation such as Proband show promise for improving risk assessment accuracy and quality patient care.     

The Effectiveness of Family History Questionnaires in Cancer Genetic Counseling

The number of individuals receiving genetic counseling for hereditary breast and ovarian cancer syndrome has steadily risen. To triage patients for genetic counseling and to help reduce the amount of time needed by a genetic counselor in direct patient contact, many clinics have implemented the use of family history questionnaires. Although such questionnaires are widely used, scant literature exists evaluating their effectiveness. This article explores the extent to which family history questionnaires are being used in Ontario and addresses the utility of such questionnaires in one familial cancer clinic. By comparing the pedigrees created from questionnaires to those updated during genetic counseling, the accuracy and effectiveness of the questionnaires was explored. Of 121 families recruited into the study, 12% acquired changes to their pedigree that led to a revised probability estimate for having a BRCA1 or BRCA2 mutation and 5% acquired changes that altered their eligibility for genetic testing. No statistically significant difference existed between the eligibility for genetic testing prior to and post counseling. This suggests that family history questionnaires can be effective at obtaining a family history and accurately assessing eligibility for genetic testing. Based on the variables that were significantly associated with a change in probability estimate, we further present recommendations for improving the clarity of such questionnaires and therefore the ease of use by patients.     

Death in the Family: Adapting a Family Systems Framework to the Grief Process

This paper presents a framework for adapting a family systems approach to the grief process. The framework places the bereaved and therapist in the larger context. The therapist builds a relationship around each family member's unique experience with death, and uses the grief timeline to facilitate timely systemic interventions. This perspective helps the therapist navigate pitfalls and remainstrategically positioned to address grief sensitively and effectively in psychotherapy.     

Using a Family History Intervention to Improve Cancer Risk Perception in a Black Community

Few studies examine the use of family history to influence risk perceptions in the African American population. This study examined the influence of a family health history (FHH) intervention on risk perceptions for breast (BRCA), colon (CRC), and prostate cancers (PRCA) among African Americans in Pittsburgh, PA. Participants (n = 665) completed pre- and post-surveys and FHHs. We compared their objective and perceived risks, classified as average, moderate, or high, and examined the accuracy of risk perceptions before and after the FHH intervention. The majority of participants had accurate risk perceptions post-FHH. Of those participants who were inaccurate pre-FHH, 43.3%, 43.8%, and 34.5% for BRCA, CRC, and PRCA, respectively, adopted accurate risk perceptions post-FHH intervention. The intervention was successful in a community setting. It has the potential to lead to healthy behavior modifications because participants adopted accurate risk perceptions. We identified a substantial number of at-risk individuals who could benefit from targeted prevention strategies, thus decreasing racial/ethnic cancer disparities.     

Reading Between the Lines: A Comparison of Responders and Non-responders to a Family History Questionnaire and Implications for Cancer Genetic Counselling

Family history questionnaires (FHQ) are useful tools for cancer genetic counseling, providing an informational basis for pedigree construction and individualized cancer risk assessment. Reported return rates of mailed FHQs amongst familial cancer clinics that utilize them are lower than desired however, and it is unknown whether patients perceive required completion of a FHQ as a barrier to access of cancer genetics services. This study critically evaluated the use of a mailed FHQ for all routine new patient referrals to a single hereditary cancer clinic in Quebec, Canada. Reasons for response/non-response to a FHQ and the effect of administration of a questionnaire on patients’ self-reported level of motivation to pursue genetic counseling, were examined. Of 112 eligible individuals referred during the study period, 86 completed a semi-structured telephone survey; of these, 45% had returned the mailed FHQ prior to the telephone survey (Responders) and 55% had not (Non-responders). Overall, the majority of participants indicated a FHQ is an acceptable and understandable method of collecting family history information. Most prevalent reasons for not returning the FHQ were (bad) timing (56%), and difficulty accessing family history information (46%). Non-response was significantly associated with difficulty in asking relatives for the requested information (p = 0.011), and Non-responders cited fewer overall perceived benefits of cancer genetic counseling as compared with Responders (p < 0.0001). One quarter of Non-responders returned the mailed FHQ following administration of the telephone survey, suggesting implementation of a follow-up prompt is a cost-effective way to increase response.     

Cancer Genetics Service Interest in Women with a Limited Family History of Breast Cancer

Women with a limited family history of breast cancer may be interested in cancer genetics information although their objective risk of breast cancer may not indicate routine referral to cancer genetics services. This study examined factors related to interest and use of cancer genetics services in a community sample of women with a limited family history of breast cancer (N = 187) who had no previous contact with cancer genetics services. Participants provided demographic information and ratings of perceived risk, cancer distress, attitudes, and intentions to initiate cancer genetics services. Participants were given information about a cancer genetics clinic that served women having concerns about their breast cancer risk. Women were contacted within 6 weeks and 8 months following their study appointment. Six weeks following their study appointment, 25% of women had initiated cancer genetics services. Eight months following their study appointment, 18% of women reported having completed a cancer genetics service appointment. Baseline intentions independently predicted both initiation at 6 weeks and appointment at 8 months. Cancer distress was positively associated with cancer genetics service initiation and appointment. Results suggest that some women with a limited family history of breast cancer are interested in seeking out cancer genetics information. Women with a limited family history of breast cancer may benefit from the availability of cancer genetics information provided through primary healthcare settings.     

Evaluation of a Heredofamilial Cancer Unit in Increasing Family History Collection and Genetic Counseling Referrals Among Spanish Oncologists at a University Hospital

A comprehensive family history is essential to identify patients at risk for hereditary cancer who could benefit from genetic counseling (GC). In a previous study, we observed a low occurrence of family history record (FHR) collection rate and GC referral among oncologists at our institution. The present work analyzes whether the implementation of a heredofamilial cancer unit (HFCU) would improve these parameters. We retrospectively compared the FHR rate in clinical records, National Cancer Institute (NCI) general criteria for hereditary cancer suspicion, GC referrals and FHR quality in two cohorts: cohort 1 (patients diagnosed before HFCU creation) and cohort 2 (after HFCU creation). Of 1,175 patients (590 cohort 1 and 585 cohort 2), FHRs were consigned in 27.3 % and 52.5 % of patients, respectively (p?<?0.001). The GC referral of patients with any NCI criterion was 13.6 % xin cohort 1 vs. 40.5 % in cohort 2 (p?<?0.001). FHR quality improved in terms of the total number of relatives (164 vs. 314, p?=?0.1, N.S.) and number of healthy relatives consigned (80 vs. 191, p?<?0.01). Nine mutations (6 BRCA, 1 MEN1, 2 Lynch), 4 unknown significance variants (all in BRCA) and 2 with no mutation were identified among patients referred from cohort 2. We conclude that the creation of a heredofamilial cancer unit has changed both FHR and GC referrals among oncologists at our institution, although continuous educational efforts are required.     

Motivations for Self‐Injury,Affect, and Impulsivity: A Comparison of Individuals with Current Self‐Injury to Individuals with a History of Self‐Injury

Individuals who report nonsuicidal self‐injury (NSSI) are characterized by the tendency to act rashly while experiencing distress (negative urgency), the tendency to act without thinking, and endorsement of both social and affect regulation motives for the behavior. However, very little research has identified characteristics that distinguish current self‐injurers from those with a history of the behavior. The purpose of this study was to compare individuals with current self‐injury to a history of self‐injury on impulsivity‐related personality traits, motives for self‐injury, and distress. Among a sample of 429 undergraduates, 120 reported self‐injury. Among these 120 individuals, 33 endorsed self‐injury within the past month, with a mean frequency of 4.77 acts of NSSI. Within the self‐injury group, current self‐injurers reported higher endorsement of affect regulation motives for NSSI, and higher levels of current negative affect than individuals with a history of self‐injury. There were no differences between current and former self‐injurers on measures of impulsivity, endorsement of social motives for NSSI, or positive affect. We propose that individuals who use NSSI to regulate negative affect may be more likely to repeatedly engage in this behavior over time.     

Accuracy of Reported Family History and Effectiveness of Medical Record Requests in Genetic Counseling for Alzheimer Disease

The University of British Columbia Hospital Clinic for Alzheimer Disease and Related Disorders (UBCH-CARD) invests significant effort to obtain medical records for the confirmation of patient–reported family histories of dementia. The effectiveness of requesting these records was assessed through a review of the 275 requests made by UBCH-CARD genetic counselors during the 24-month period of January 1, 2005–December 31, 2006. The results were categorized according to outcome. Useful medical records were obtained from 92 (33.5%) requests: 77 (28%) records supported, and 15 (5.5%) records did not support, the patient–reported information. An additional 20 (7.5%) requests yielded only vague information. When verification was possible, patient–reported family histories of Alzheimer disease, dementia, or memory loss were accurate in 84% of cases. During the study period, almost 500 h of genetic counselor work time was spent obtaining, reviewing, and following-up on records received. Changes made to UBCH-CARD procedure in response to these findings are discussed.