Further defining the roles and impact of genetic counselors in the biotechnology and pharmaceutical industry.

As personalized medicine has gained traction, drug development models in the biotechnology and pharmaceutical industry (BPI) have increasingly sought to address medical conditions with a genetic component, creating an opportunity for genetic counselors (GCs) to fill new roles and utilize their unique training to contribute to drug development. Despite the potential for GCs in BPI, literature around the role of GCs in this industry has been limited. Our mixed methods study aimed to assess how the roles of GCs in BPI have evolved since 2016, investigate the value of and opportunity for GCs in this industry, and further characterize their motivation and job satisfaction. Participants were recruited via social media advertising, snowball sampling, and email listservs from the National Society of Genetic Counseling (NSGC), the Canadian Association of Genetic Counselors (CAGC), and the American Board of Genetic Counseling (ABGC). Survey (n = 20) and interview (n = 6) data indicates many aspects of GC roles in BPI are consistent with the 2016 study. However, there is evidence of roles becoming more varied and with increasing recognition of the value of GCs, opportunities for involvement in BPI are growing. Furthermore, combined study data found that GCs are motivated by the flexibility of BPI roles as well as the opportunity to contribute to rare disease treatment development and that they are overall satisfied with most aspects of their jobs. Interview data also found that genetic counseling training has the potential to improve clinical trial design and outcomes by making drug development more patient-centric. Finally, combined study data found that while GCs continue to utilize Accreditation Council of Genetic Counseling (ACGC) practice-based competencies (PBCs), business-related training may benefit GCs seeking to enter BPI. Together, these findings are critical for informing genetic counseling training programs, employers within BPI, and GCs interested in entering these positions.

Genetic counseling graduate program faculty perspectives on sharing education materials among programs.

Rapid advancements in genetics care requires responsive genetic counseling (GC) training capable of integrating new discoveries and practice into their curricula. The utilization of shared or standardized educational resources may address this need. Recognizing the potential of shared resources, the Pharmacogenetics (PGx) Working Group of the NSGC Precision Medicine Special Interest Group (SIG) launched a standardized education module using a flipped-classroom format to provide all GC programs equal access to PGx expertise and alleviate the burden of curriculum development. Following the initial success of the program, we aimed to explore the utilization of shared and standardized education resources more broadly, and better understand the perspectives of GC program faculty regarding their use. Twenty-nine program faculty representing at least 14 programs responded to an online survey. The majority (n = 21) reported sharing educational materials with another GC program, and 90% of those reported the shared materials to be beneficial as they promote collaboration, efficiency, address a gap in content, and provide access to experts. Similar benefits were described when using a standardized curriculum, which was defined as standardized lectures and activities created about a particular topic and made available to all genetic counseling programs; 16 participants indicated they would be very likely or likely to use a standardized curriculum. A secondary aim of the survey was to assess the existing PGx module that utilizes a flipped-classroom format. Overall, the PGx module was well received, indicating that a standardized shared module is well-suited for instruction on emerging and specialty topics. All participants believed the flipped-classroom format to be very or somewhat beneficial. In summary, results indicate that shared educational materials, including standardized education modules, are a potential solution to challenges related to efficiency and access to content experts in GC education, and program leadership is receptive to using them.

An examination of psychosocial and professional effects of the COVID-19 pandemic on genetic counselors.

For healthcare workers, recognized professional challenges associated with the COVID-19 pandemic include changes to service delivery models, increased burnout, furlough, and loss of income. The main goal of this study was to more clearly define the impact on mental health and quality of life of genetic counselors during the COVID-19 pandemic in the contexts of their personal, professional, and social lives. Eligible genetic counselors (GCs) (n = 283) responded to an online survey that incorporated validated instruments: Patient Health Questionnaire, Generalized Anxiety Disorder, Professional Quality of Life, and the In Charge Financial Distress/Financial Well-Being Scale. Additionally, original questions were developed from previous qualitative research on COVID-19 challenges for healthcare workers. Results showed 62% of respondents felt their mental health was impacted for the worse, 45% found it more difficult to achieve work/life balance, 16.8% scored within moderate-to-severe depression severity, 19.2% scored within moderate-to-severe anxiety, 26.3% reported high burnout, and 7% had high financial distress. GCs reported generally lower levels of anxiety and depression compared to healthcare workers and the general population. Thematic analysis identified feelings of isolation and difficulties balancing professional/personal responsibilities with more remote work. However, some participants reported greater flexibility in their schedule and more time with family. Self-care activities increased, with 93% engaging in more meditation and 54% began exercising. There were similar themes reported in this survey compared to other healthcare workers' experiences. There is also a dichotomy in positive and negative impacts with some GCs appreciating the flexibility of working from home but others reporting this blurs the line between personal and professional responsibilities. These results suggest consequences of the COVID-19 pandemic will continue to impact the field of genetic counseling and understanding these changes will be instrumental in addressing the needs of GCs to practice effectively.

Motivation and family communication in hereditary prostate cancer genetic testing: Survey of patients from a US tertiary medical center.

Identification of a hereditary prostate cancer in an affected individual can guide treatment and may also impact cancer screening and surveillance for patients and their relatives. This study aimed to determine the factors that are associated with the decision-making process of individuals with prostate cancer regarding whether to pursue genetic testing as well as how, why, and with whom genetic test results are shared. We surveyed 113 patients diagnosed with prostate cancer who received cancer genetic counseling through a United States tertiary medical center, inquiring about genetic testing motivations and family communication about results. Among those who pursued genetic testing, (1) learning about my family's possible cancer risk (98%), (2) learning information that may guide cancer treatment (93%), and (3) learning if I am at risk for future cancers (92%) were most frequently identified as slightly or very important factors in their decision. Participants shared their genetic test results in a higher proportion to male first-degree relatives than female first-degree relatives; however, no significant difference was found (p = 0.103). Our study may suggest sex differences related to family communication about genetic testing results. Such findings indicate a critical need for genetic counselors to clearly communicate the impact of genetic test results on both male and female relatives. Further research on motivation and family communication about genetic test results in diverse cohorts is needed.

Genetic testing to gain diagnostic clarity in neurofibromatosis type 2 and schwannomatosis.

Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) have distinct genetic etiologies but overlapping phenotypes. Genetic testing may be required for accurate diagnosis, which is critical for determining prognosis, screening recommendations, and treatment options. Our study aimed to compare the efficacy of germline-only versus paired (germline and tumor) genetic testing for clarifying the diagnosis in patients with features of NF2 and SWN. We performed a retrospective chart review of patients referred for NF2/SWN genetic testing at Massachusetts General Hospital from 2015 to 2020. Logistic regression analysis was performed to assess factors associated with diagnostic clarity. Overall, paired testing had 8.5 times greater odds of providing diagnostic clarity than germline-only testing (p < 0.01). Among patients who underwent paired testing, those who had analysis of two or more tumors had the greatest likelihood of gaining diagnostic clarity, with odds 13 times greater than patients who underwent germline-only testing (p < 0.01). Paired testing with analysis of one tumor significantly increased the odds of diagnostic clarity over germline-only testing by a factor of 6.5 (p < 0.01). These results have implications for genetic testing strategies and counseling patients about genetic testing utility. They also support the routine use of testing in individuals with suspected NF2 or SWN and improved insurance coverage for paired testing within this population.

A patient-centered mobile health application to motivate use of genetic counseling among women with ovarian cancer: A pilot randomized controlled trial.

OBJECTIVE: Despite current guidelines recommending women with ovarian cancer receive genetic risk evaluation by a genetic counselor, utilization has historically been low. We sought to assess the feasibility and effectiveness of a week-long mobile Application for Genetic Information on Cancer (mAGIC) intervention aimed to persuade women with ovarian cancer to pursue genetic counseling. METHODS: The mobile application intervention was based on the Fogg Behavior Model, and consisted of three parts: (1) identifying barriers, (2) developing motivators, and (3) providing triggers to action. The Health Belief Model was used to guide content development. We conducted a prospective, randomized, controlled pilot trial among 104 untested women with a history of epithelial ovarian, primary peritoneal or fallopian tube cancer with the primary objective of increasing uptake of cancer genetic counseling services. RESULTS: Utilization of cancer genetic counseling services improved in both study arms over historical controls, however there was no statistically significant difference between them (intervention: 54.5% versus control: 38.6%; p = 0.14). However, compared to controls, women randomized to the mAGIC intervention demonstrated greater knowledge of hereditary cancer (0-10 scale; 9.4 ±â€¯1.0 vs. 7.1 ±â€¯1.5; p < 0.0001), which persisted for at least three months. Additionally, 96% of women in the intervention group reported they had talked with their family about genetic counseling compared to 77% in the control group (p = 0.01). CONCLUSIONS: The mAGIC intervention did not result in increased uptake of genetic counseling, however it provided significant secondary benefits, including increased participants' knowledge about hereditary ovarian cancer, self-efficacy, and their reported communication with family members. ClinicalTrials.gov Identifier: NCT02877862.

A qualitative study of barriers to genetic counseling and potential for mobile technology education among women with ovarian cancer.

BACKGROUND: National guidelines recommend genetic counseling for all ovarian cancer patients because up to 20% of ovarian cancers are thought to be due to hereditary cancer syndromes and effective cancer screening and prevention options exist for at-risk family members. Despite these recommendations, uptake of genetic counselling and testing is low. The goal of this study was to identify barriers to and motivators for receipt of genetic counseling along with preferences regarding potential use of a mobile application to promote genetic counseling. METHODS: Three focus groups were conducted including 14 women with a diagnosis of epithelial ovarian, primary peritoneal or fallopian tube cancer. Topics included understanding of genetic counseling, perceived pros and cons, preferences for receiving health information, and familiarity with mobile phone technology. Transcripts were analyzed using standard procedures of qualitative thematic text analysis and descriptive coding techniques. RESULTS: Six major themes regarding barriers to and motivators of genetic counseling and use of mobile technology in promoting genetic counseling emerged: (1) need for information, (2) relevance, (3) emotional concerns, (4) family concerns, (5) practical concerns, and (6) mobile application considerations. CONCLUSIONS: These data reiterate previously reported barriers to genetic counseling as observed in other populations. Participants were supportive of the use of mobile technology for promoting uptake of genetic counseling.

A model for patient-direct screening and referral for familial cancer risk.

Patients at increased familial risk of cancer are sub-optimally identified and referred for genetic counseling. We describe a systematic model for information collection, screening and referral for hereditary cancer risk. Individuals from three different clinical and research populations were screened for hereditary cancer risk using a two-tier process: a 7-item screener followed by review of family history by a genetic counselor and application of published criteria. A total of 869 subjects participated in the study; 769 in this high risk population had increased familial cancer risk based on the screening questionnaire. Of these eligible participants, 500 (65.0 %) provided family histories and 332 (66.4 %) of these were found to be at high risk of a hereditary cancer syndrome, 102 (20.4 %) at moderate familial cancer risk, and 66 (13.2 %) at average risk. Three months following receipt of the risk result letter, nearly all respondents found the process at least somewhat helpful (98.4 %). All participants identified as high-risk were mailed a letter recommending genetic counseling and were provided appointment tools. After 1 year, only 13 (7.3 %) of 179 high risk respondents reported pursuit of recommended genetic counseling. Participants were willing to provide family history information for the purposes of risk assessment; however, few patients pursued recommended genetic services. This suggests that cancer family history registries are feasible and viable but that further research is needed to increase the uptake of genetic counseling.

What's the harm? Genetic counselor perceptions of adverse effects of genetics service provision by non-genetics professionals.

Anecdotal accounts suggest some patients have experienced negative outcomes as a result of receiving genetics services from non-genetics providers, but empirical evidence of these incidents and their outcomes is limited. This study examined genetic counselors' perceptions of the occurrence of such incidents in the state of Minnesota. Twenty-five genetic counselors completed an on-line survey and 20 also participated in a semi-structured telephone interview. The interviewees recalled and described 37 specific incidents they perceived as having negative outcomes for patients and/or their families. Inductive and cross-case analysis revealed common themes including: adverse psychosocial effects, inadequate genetic counseling, genetic testing and screening errors, medical mismanagement, negative shifts in attitudes toward medical providers, and unnecessary use of health care resources. Commonly mentioned strategies for preventing/mitigating negative outcomes included: educational outreach and awareness programs for medical providers and the general public, standardized testing and screening processes, and implementing mechanisms for reporting and addressing adverse events. Additional findings, practice and policy implications, and research recommendations are discussed.

Estimating CDKN2A carrier probability and personalizing cancer risk assessments in hereditary melanoma using MelaPRO.

Personalized cancer risk assessment remains an essential imperative in postgenomic cancer medicine. In hereditary melanoma, germline CDKN2A mutations have been reproducibly identified in melanoma-prone kindreds worldwide. However, genetic risk counseling for hereditary melanoma remains clinically challenging. To address this challenge, we developed and validated MelaPRO, an algorithm that provides germline CDKN2A mutation probabilities and melanoma risk to individuals from melanoma-prone families. MelaPRO builds on comprehensive genetic information, and uses Mendelian modeling to provide fine resolution and high accuracy. In an independent validation of 195 individuals from 167 families, MelaPRO exhibited good discrimination with a concordance index (C) of 0.86 [95% confidence intervals (95% CI), 0.75-0.97] and good calibration, with no significant difference between observed and predicted carriers (26; 95% CI, 20-35, as compared with 22 observed). In cross-validation, MelaPRO outperformed the existing predictive model MELPREDICT (C, 0.82; 95% CI, 0.61-0.93), with a difference of 0.05 (95% CI, 0.007-0.17). MelaPRO is a clinically accessible tool that can effectively provide personalized risk counseling for all members of hereditary melanoma families.

Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts.

The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early-onset disease; functionally characterized new variants and conducted a population-based case-control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2-H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2-1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early-onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2-positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2-P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low-penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically- and geographically-selected populations.

High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL.

GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, c.IVS2-105A>G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available.

Healthy women with a family history of breast cancer: impact of a tailored genetic counseling intervention on risk perception, knowledge, and menopausal therapy decision making.

BACKGROUND: Women with a family history of breast cancer have several menopausal therapy options, including tamoxifen, hormone therapy (HT), alternative medications, or no treatment. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. The authors determined the effects of a personalized risk assessment and genetic counseling intervention on knowledge, risk perception, and decision making in a group of healthy women who had a first-degree relative with breast cancer. METHODS: Forty-eight cancer-free menopausal women age > or =40 years who had at least one first-degree relative with breast cancer were randomized to a genetic counseling intervention or control. Intervention participants were given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data. Knowledge, risk perception, and medication usage were measured at baseline, 1 month, and 6 months. RESULTS: Knowledge was higher in the intervention group at both follow-up time points postintervention. Perceived risk for developing breast cancer was significantly lower and more accurate in the intervention group at 1 and 6 months postintervention than at baseline, as was perceived risk of developing heart disease. Although the counseling intervention did affect both knowledge and risk perception, overall, both groups were reluctant to take any form of menopausal therapy. CONCLUSIONS: A personalized risk assessment and genetic counseling intervention improves patient knowledge and risk perception; however, it is unclear that the intervention influenced menopausal treatment decisions.

Cutaneous melanoma: family screening and genetic testing.

The incidence of cutaneous melanoma (CM) has been steadily increasing in recent decades. Ultraviolet radiation (UVR) exposure, in the form of intermittent heavy exposure and severe sunburns in childhood, is believed to be the most important environmental contribution to CM risk. Genetic determinants also modulate CM risk, probably to a greater extent than environmental exposure. Certain heritable traits such as prominent numbers of common and atypical melanocytic nevi, skin type, dense UVR-induced freckling, and hair color are all known to be associated with increased CM risk. Very rarely, a heritable mutation in a high-risk gene renders the susceptible individual at extreme risk for CM. Families may carry one or more of the other high-risk phenotypic traits leading to uncertainty about how to quantify CM risk and provide management recommendations. Commercial genetic testing for the known high-risk inherited genetic mutations is available but is only relevant for those rare families likely to be carrying identifiable mutations. CM screening and risk intervention programs are being established internationally for families at markedly increased risk. Algorithms based on the level of risk are proposed.

Correlation of polyp number and family history of colon cancer with germline MYH mutations.

BACKGROUND & AIMS: Affected individuals with biallelic MYH mutations are believed to display multiple adenomatous polyps without evidence of vertical transmission. Our goal was to determine the detection rate of germline MYH mutations in a high-risk gastrointestinal cancer clinic population by using polyp number as a selection criterion. METHODS: Patients were screened for the 2 most common MYH mutations: Y165C and G382D. The complete MYH coding region was sequenced in cases with a heterozygous mutation. RESULTS: Among 45 patients with more than 15 adenomatous polyps not diagnosed with familial adenomatous polyposis, 7 (15.6%) had biallelic MYH mutations. When 122 participants from a high-risk gastrointestinal cancer clinic who did not fulfill these criteria were tested, 2 additional patients with biallelic mutations were identified. Both had young-onset colorectal cancer (age, <50 y) with fewer than 15 polyps. Surprisingly, most of the 9 patients with biallelic MYH mutations reported family histories consistent with the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), with 7 cases meeting at least 1 of the Bethesda criteria, 5 cases fulfilling 3 Bethesda criteria, and 2 cases fulfilling the Amsterdam II criteria. CONCLUSIONS: Most individuals with MYH mutations exhibit multiple adenomatous polyps. However, 22% of cases were missed when this was the sole criterion for germline testing. A significant number reported a strong family history of cancer that was consistent with HNPCC. MYH testing thus can be considered for patients who meet clinical criteria for HNPCC in the absence of DNA mismatch repair gene mutations.

Hereditary cancer syndromes of the skin.

Hereditary cancer syndromes are a group of disorders characterized by a genetic susceptibility to the development of malignant tumors. Multiple cancers in the family or an abnormally early onset for the given cancer may suggest an underlying inherited predisposition. Awareness of their associated dermatologic manifestations can facilitate early detection of risk for neoplasms. This article provides an update on the clinical features, diagnostic criteria, and the use of genetic analysis in the detection of causative mutations of those hereditary cancer syndromes with cutaneous manifestations.

Genetic testing in hereditary melanoma.

Advances in our understanding of molecular genetics bring about unique challenges in our ability to practice molecular medicine. With the availability of commercial testing for various genetic cancer syndromes, including hereditary melanoma, specific issues regarding its use and limitations require attention before full translation of this tool into the clinical setting.

A novel methionine-53-valine mutation of p16 in a hereditary melanoma kindred.

We report a novel germline Met53Val mutation in CDKN2A from a large melanoma-prone family; this mutation occurs in exon 2 of CDKN2A where p16 and alternative reading frame (ARF) both share transcript sequences. The previously reported Met53Ile and the current Met53Val mutations are coupled to distinct Asp68His and Asp67Gly alterations in ARF, respectively. The coincidence of second, independent p16 Met53 alteration that differentially alters ARF suggests that there may be selectivity for targeting the p16 transcript over the ARF transcript.

Developing Standard Recommendations (Guidelines) for Genetic Counseling Practice: A Process of the National Society of Genetic Counselors.

The National Society of Genetic Counselors (NSGC) supports the development of practice recommendations (guidelines) in the field of genetic counseling. This paper reviews the basic components of NSGC genetic counseling practice recommendations as well as the process for formal adoption of such documents, as approved by the Board of Directors of the NSGC.