Genetic testing

Genetic Counseling and Testing for Pulmonary Arterial Hypertension in the United States

Disparities in completion of genetic testing and counseling for Lynch syndrome in high-risk patients diagnosed with endometrial cancer (601)

Background: Roughly 7–10% of patients with pancreatic ductal adenocarcinoma (PDAC) have a deleterious germline variant. Although identification of germline variants in family members has implications for cancer surveillance and can lead to early cancer detection and interception for PDAC, as well as other cancers, cascade genetic testing rates are low. The GENetic Education, Risk Assessment and TEsting (GENERATE) study evaluates novel methods of providing genetic education and testing for individuals at risk for hereditary PDAC. Methods: Eligible participants had: (1) a first- or second-degree relative with a diagnosis of PDAC and a known familial germline variant in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53 (Known Familial Mutation (KFM)), (2) or were first-degree relatives of PDAC patients (no KFM). Participants were recruited through six academic centers, patient advocacy organizations and online outreach. Enrollment occurred through the study website (www.GENERATEstudy.org). All study participation, including genetic testing via a at home saliva sample kit, was done remotely. Participants were cluster randomized at the family level into one of two arms. Arm 1 (Doxy.me plus Color Genomics) included remote genetic education and testing through a video-based telemedicine platform (Doxy.me) and physician-mediated testing through Color Genomics. Arm 2 included remote genetic education and testing through Color Genomics only. Results: Between 5/8/2019–6/01/2021, 423 families were randomized, comprising 595 participants. Recruitment occurred through patient invitation via healthcare providers (n=128, 21.5%), family members (n=271, 45.5%), friends, advocacy groups, and online outreach (n=223, 37.5%). Participants were referred from the six GENERATE academic centers (n=270, 45.4%) and other institutions (n=325, 54.6%). Study participants were 52.5 years on average, primarily identified as White (n=577, 97%) and from the Northeast (n=184, 30.9%), Midwest (n=154, 25.9%), South (n=158, 26.6%) and West (n=99, 16.6%). Participants were randomized into each arm (n=296 Doxy.me plus Color Genomics; n=299 Color Genomics only). To date, 527 (88.6%) participants have ordered genetic testing. The uptake of genetic testing was 253/296 (85.5%) in the Doxy.me plus Color Genomics arm and 274/299 (91.6%) in the Color Genomics only arm (p=0.049, generalized mixed-effects model). A total of 82 PDAC associated pathogenic variants were identified. The most frequently detected variants were BRCA2 (n=32), ATM (n=25) and PALB2 (n=6). Additionally, 13 non-PDAC associated pathogenic variants and 20 low penetrance variants were detected. Conclusions: Remote methods of genetic education and testing are successful alternatives to traditional cascade testing, with genetic testing rates nearly 90%. Participant follow up will assess if satisfaction with decision making, cancer-risk distress, knowledge gained, family communication, and uptake of surveillance were impacted by the mode of delivery of pre-test genetic education. Citation Format: Nicolette J. Rodriguez, Constance S. Furniss, Matthew B. Yurgelun, Chinedu Ukaegbu, Pamela E. Constantinou, Alison N. Schwartz, Jill Stopfer, Meghan Underhill-Blazey, Barbara Kenner, Scott Nelson, Sydney Okumura, Sherman Law, Alicia Y. Zhou, Tara B. Coffin, Hajime Uno, Allyson Ocean, Florencia McAllister, Andrew M. Lowy, Scott M. Lippman, Alison P. Klein, Lisa Madlensky, Gloria M. Petersen, Judy E. Garber, Michael G. Goggins, Anirban Maitra, Sapna Syngal. Comparison of novel healthcare delivery models on the uptake of genetic education and testing in families with a history of pancreatic cancer: The GENetic Education, Risk Assessment and TEsting (GENERATE) study [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-013.

Objective: New medical discoveries regarding genetic susceptibility to common chronic diseases, and the decoding of the human genome have increased public attention to genetics. What information is understood and what attitudes exist towards genetics and genetic research have not been well examined in underserved, culturally diverse communities. Methods: To better understand attitudes and beliefs towards genetics and genetic testing in these groups, we conducted eight focus groups with 55 patients and health care workers in New York City and Westchester, N.Y., in English, Spanish, and Chinese. Results: Focus group participants had limited understanding about genetics or genetic testing. Newborn screening was the least-known genetic issue, even among health care workers. Regardless of their cultural group, most participants expressed a desire for more information about genetics and genetic tests. Latinos and Chinese participants generally expressed positive attitudes towards genetic studies and genetic testing, with the possibility of preventing diseases cited as the main advantage. Black Americans and Non-Hispanic Whites reported mixed feelings about genetic research and genetic testing. Concerns expressed included: anxiety before receiving test results or waiting for a disease to develop, fear of genetic discrimination by health and life insurance companies and employers, not having the financial means to deal with genetic diseases in themselves or a sick child, concern that children and adults are having too many tests. Black Americans expressed the most concern for possibly harmful use of genetic information. Conclusions: Minority populations of diverse cultures have limited knowledge about genetics and genetic testing, would like to have more information, and are not well reached by the current educational approaches. Participants knew the least about newborn screening, a test that is mandatory in the New York State. While genetic knowledge by minority populations was perhaps not different from the level of knowledge of consumers in general, minority populations are at particular risk of being left behind because of historically poor access to information and services.

Genetic counseling and testing for hereditary cancer risk in young adult women: Facilitating autonomy and informed decision making is key

<div>Abstract<p>Up to 10% of patients with pancreatic ductal adenocarcinoma (PDAC) carry underlying germline pathogenic variants in cancer susceptibility genes. The GENetic Education Risk Assessment and TEsting (GENERATE) study aimed to evaluate novel methods of genetic education and testing in relatives of patients with PDAC. Eligible individuals had a family history of PDAC and a relative with a germline pathogenic variant in <i>APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11</i>, or <i>TP53</i> genes. Participants were recruited at six academic cancer centers and through social media campaigns and patient advocacy efforts. Enrollment occurred via the study website (<a href="https://GENERATEstudy.org" target="_blank">https://GENERATEstudy.org</a>) and all participation, including collecting a saliva sample for genetic testing, could be done from home. Participants were randomized to one of two remote methods that delivered genetic education about the risks of inherited PDAC and strategies for surveillance. The primary outcome of the study was uptake of genetic testing. From 5/8/2019 to 5/6/2020, 49 participants were randomized to each of the intervention arms. Overall, 90 of 98 (92%) of randomized participants completed genetic testing. The most frequently detected pathogenic variants included those in <i>BRCA2</i> (<i>N</i> = 15, 17%), <i>ATM</i> (<i>N</i> = 11, 12%), and <i>CDKN2A</i> (<i>N</i> = 4, 4%). Participation in the study remained steady throughout the onset of the Coronavirus disease (COVID-19) pandemic. Preliminary data from the GENERATE study indicate success of remote alternatives to traditional cascade testing, with genetic testing rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for PDAC interception approaches.</p>Prevention Relevance:<p>Preliminary data from the GENERATE study indicate success of remote alternatives for pancreatic cancer genetic testing and education, with genetic testing uptake rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for pancreatic cancer interception.</p></div>

Colorectal Cancer Genetics Screening in the Community: Are We Ready? Can We Do It?

Background. Breast cancer is a devastating disease. Identification of the BRCA1 and BRCA2 genetic mutations associated with it offer to provide an efficacious “early warning system”. However investigators question whether women are interested in knowing if they possess gene mutations, particularly minorities traditionally averse to dealing with a complex medical system. Effective means for addressing these gaps are unidentified. Here we determine the extent of interest in genetic testing among Latinas compared to Non-Hispanic White (NHW) women. Also, we identify factors associated with interest in genetic testing. Finally, we show why differences in interest in genetic testing for breast cancer exist among groups of women. Material and Methods. We surveyed 290 women (153 Hispanic, 137 NHW) aged 26+ from the San Antonio Cancer Therapy and Research Center's catchment area. Surveys included demographic information, measures assessing breast cancer knowledge, attitudes, behaviors, and medical and family history data. Participants were assigned “high” or “moderate/low” cancer risk status according to American College of Medical Genetics Foundation guidelines. Chi-Square and Student's T-tests assessed bivariate relationships. Multivariate logistic regression identified factors associated with interest in genetic testing. Results. 20% of women were not “Very interested” in genetic testing for the BRCA1/BRCA2 mutation. Bivariate results showed ethnicity, use of non-traditional health care sources and negative perceptions of genetic testing were associated with low interest in genetic testing among all women. A multivariate model of genetic testing interest revealed several measures significantly associated with it, including Hispanic ethnicity (OR 5.74, p<.01), routine health care from any non-traditional source and negative perception of genetic testing (both OR 1.19, p<.03). The Hispanic result reflected reduced interested in Genetic Testing, regardless cancer risk or having had cancer [Low-risk Latinas: 75.3% v 84.9% NHW (p<.05); High-risk Latinas 75.3% v 84.9% NHW (p<.05), Cochran Mantel-Haenszel (CMH) ns.], [NoHx of Cancer Latinas 75.6% v 90.2% p<.04, Hx Cancer Latinas 72.0% v 82.9%, p<.05, CMH ns.] Given this difference we stratified our analysis. In separate multivariate models we found that NHW women are not “very interested” in genetic testing when their perception of it is negative (OR 1.36, p<.01). Latinas are significantly more likely to be interested in genetic testing when their perceived risk of breast cancer is high (OR 2.38, p<.01), and importantly, when they have biological daughters (OR 7.85, p<.001). 77.8% of Latinas with biological daughters (n = 98) compared to 55.6% of those without (n = 61) were “Very interested” in genetic testing for breast cancer (p<.001). Conclusion: Genetic testing is generally acceptable to NHW and Hispanic women. However, Latinas are less likely to accept it than NHW. Whereas NHW women are influenced in their decision chiefly by use of nontraditional sources of medical care, Latinas are strongly influenced by perceptions of personal risk and having biological daughters. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-04.

AimsCardiomyopathies comprise a heterogeneous group of diseases, often of genetic origin. We assessed the current practice of genetic counselling and testing in the prospective European Society of Cardiology EURObservational Research Programme Cardiomyopathy Registry.Methods and resultsA total of 3208 adult patients from 69 centres in 18 countries were enrolled. Genetic counselling was performed in 60.8% of all patients [75.4% in hypertrophic cardiomyopathy (HCM), 39.2% in dilated cardiomyopathy (DCM), 70.8% in arrhythmogenic right ventricular cardiomyopathy (ARVC), and 49.2% in restrictive cardiomyopathy (RCM), P < 0.001]. Comparing European geographical areas, genetic counselling was performed from 42.4% to 83.3% (P < 0.001). It was provided by a cardiologist (85.3%), geneticist (15.1%), genetic counsellor (11.3%), or a nurse (7.5%) (P < 0.001). Genetic testing was performed in 37.3% of all patients (48.8% in HCM, 18.6% in DCM, 55.6% in ARVC, and 43.6% in RCM, P < 0.001). Index patients with genetic testing were younger at diagnosis and had more familial disease, family history of sudden cardiac death, or implanted cardioverter defibrillators but less co‐morbidities than those not tested (P < 0.001 for each comparison). At least one disease‐causing variant was found in 41.7% of index patients with genetic testing (43.3% in HCM, 33.3% in DCM, 51.4% in ARVC, and 42.9% in RCM, P = 0.13).ConclusionsThis is the first detailed report on the real‐life practice of genetic counselling and testing in cardiomyopathies in Europe. Genetic counselling and testing were performed in a substantial proportion of patients but less often than recommended by European guidelines and much less in DCM than in HCM and ARVC, despite evidence for genetic background.

Few studies have quantitatively evaluated the uptake and outcomes of BRCA1/2 genetic counseling and testing in men. We conducted a prospective longitudinal study to describe and compare uptake of and psychosocial outcomes following BRCA1/2 testing in a sample of men and women at high-risk for carrying a BRCA1/2 mutation. Men (n=98) and women (n=243) unaffected with cancer completed baseline assessments prior to genetic counseling and testing and then 6- and 12-months post-testing. Most men (n=94; 95.9%) opted to have genetic testing, of whom 44 received positive BRCA1/2 genetic test results and 50 received true negative results. Among women, 93.4% had genetic testing, of whom 79 received positive results and 148 received negative results. In multivariate models, male BRCA1/2 carriers reported significantly higher genetic testing distress (6-months: Z=4.48, P<0.0001; 12-months: Z=2.78, P<0.01) than male non-carriers. After controlling for baseline levels of distress, no statistically significant differences emerged between male and female BRCA1/2 carriers in psychological distress at 12-months post-testing, although absolute differences were evident over time. Predictors of distress related to genetic testing among male carriers at 12-months included higher baseline cancer-specific distress (Z=4.73, P<0.0001) and being unmarried (Z=2.18, P<0.05). Similarly, baseline cancer-specific distress was independently associated with cancer-specific distress at 6- (Z=3.66, P<0.001) and 12-months (Z=4.44, P<0.0001) post-testing among male carriers. Clinically, our results suggest that pre-test assessment of distress and creation of educational materials specifically tailored to the needs and concerns of male carriers may be appropriate in this important but understudied high-risk group.

A scoping review of the assessment reports of genetic or genomic tests reveals inconsistent consideration of key dimensions of clinical utility.

Genetic testing has a potential in the prevention of genetic diseases, particularly in communities with high rates of consanguineous marriage. Therefore, knowledge, practice, and attitudes of the public in Jordan regarding genetic testing were investigated. Individuals (N = 3,196) were questioned about the concepts of genetic testing and genetic counselors, if they underwent any genetic tests, the type of test, the method of consenting to the test, as well as their level of satisfaction with the privacy of the genetic testing service. The likelihood of pursuing predictive genetic testing for cancer was also investigated. Although almost 70 % of respondents knew the term "genetic testing," only 18 % had undergone genetic testing, primarily the mandatory premarital test. In addition, there was a lack of general knowledge about genetic counselors. Many of those who had genetic testing (45 %) indicated they did not go through a consent process, and a lack of consent was significantly related to dissatisfaction with the privacy of the service. Approximately 55 % of respondents indicated they would potentially pursue predictive genetic testing for cancer. Going for routine health checkups was not significantly correlated with either actual or potential uptake of genetic testing, suggesting health care providers do not play an influential role in patients' testing decisions. Our results show a gap between the knowledge and uptake of genetic testing and may help to guide the design of effective strategies to initiate successful genetic counseling and testing services.

Genetic testing is critical for optimal diagnosis and management of pediatric neurology patients, but access is challenging. We investigated whether social determinants of health (SDOH) were associated with genetic testing among pediatric neurology patients in a retrospective observational study. Electronic health record data were extracted from pediatric outpatients (0-18 years) evaluated at a single tertiary care institution between July 2018 and January 2020. Genetic testing requests, insurance denials, and test completion rates were compared among non-Hispanic single-racial or multiracial Black (Black) vs non-Hispanic single-racial White (White) patients. SDOH and clinical variables including ethnoracial identity, insurance type, Area Deprivation Index, rural urban commuting area, sex, age, diagnoses, and number of neurology visits were evaluated to identify associations with chromosomal microarray (CMA), multigene panel (MGP), and exome/genome sequencing (ES/GS) test completion. Of 11,371 patients (mean age 9.25 years; 46.1% female), 554 (4.9%) completed ≥1 genetic test in the study interval, with White patients nearly twice as likely to have completed ≥1 genetic test compared with Black patients (aOR 1.88, 95% CI 1.41-2.51). Outpatient pediatric neurology was the most common specialty through which testing was completed. Neurology provider request rates for genetic testing did not differ by patient ethnoracial identity, but insurance denial rates after neurology request were lower for White vs Black patients (relative rate ratio [RR] 0.44, 95% CI 0.27-0.73), and those with public insurance were less likely to complete genetic testing after it was requested through neurology (aOR 0.59, 95% CI 0.35-0.97). However, when considering individual genetic test types completed through any specialty, insurance type was significantly associated only with MGP completion (public vs private OR 0.56, 95% CI 0.40-0.77), not CMA or ES/GS. Marked ethnoracial disparities in genetic testing completion were identified despite equivalent rates of genetic testing requests by neurologists. While Black patients had higher rates of insurance denials, insurance type itself accounted for the disparity in MGP but not CMA or ES/GS completion. Other unmeasured barriers stemming from systemic racism likely affected genetic testing among Black patients.

Genetic testing for Parkinson’s disease (PD) is increasing globally, and genetic counseling is an important service that provides information and promotes understanding about PD genetics and genetic testing. PD research studies have initiated outreach to underrepresented regions in North America, including regions in Latin America, such as the Dominican Republic (DR); some studies may include return of genetic test results. Thus, understanding what individuals know about PD, genetic testing for PD, and their interest in speaking with a genetic counselor, is crucial when assessing readiness. In this cross-sectional study, a survey was distributed to people with Parkinson’s disease (PwP) and their unaffected biological relatives in the DR. Questions assessed genetics knowledge, attitude toward genetic testing, and interest in genetic testing and counseling. Of 45 participants, 69% scored the maximum on the attitude scale, indicating an overall positive attitude toward genetic testing; 95% indicated interest in genetic testing for PD, and 98% were at least somewhat interested in meeting with a genetic counselor. The mean PD genetics knowledge score was similar to previously published data. Through free text responses, participants expressed a desire to know more about PD treatment and management, prevention, cause, and their personal risk for PD. These results provide further evidence of readiness for genetic testing in this country but also underscore some gaps in knowledge that should be addressed with targeted educational efforts, as part of building genetic testing and counseling capacities.

There are limited data on the impact of incorporating genetic counseling and testing into the newborn hearing screening process. We report on results from a prospective, longitudinal study to determine the impact of genetic counseling and GJB2/GJB6 genetic testing on parental knowledge, attitudes, and beliefs about genetic testing. One hundred thirty culturally hearing parents of 93 deaf or hard-of-hearing children ages 0-3 years primarily identified through newborn hearing screening received pre- and post-test genetic counseling for GJB2 and GJB6. Parents completed questionnaires following pre-test counseling, and 1- and 6-month post-test result disclosure. Results indicate that following pre-test counseling all parents perceived benefits to genetic testing. While parents who received positive results continued to perceive benefits from testing, perceived benefit declined among parents who received inconclusive or negative results. Parents did not perceive genetic testing as harmful following pre-test counseling or receipt of test results. Parents who received positive test results performed better in understanding recurrence and causation of their child's deafness and indicated greater interest in prenatal genetic testing than those who received inconclusive or negative test results. Parents felt that pediatricians and audiologists should inform parents of genetic testing availability; however, there was no consensus on timing of this discussion. Thus culturally hearing parents do not perceive genetic testing of their deaf or hard-of-hearing infants/toddlers as harmful; they feel that primary care providers should discuss genetic testing with them; and positive genetic test results with genetic counseling give rise to better understanding and perceived benefit than negative or inconclusive results.