Factors which impact the delivery of genetic risk assessment services focused on inherited cancer genomics: expanding the role and reach of certified genetics professionals.

There is tremendous excitement about the promise of new genomic technologies to transform medical practice and improve patient care. Although the full power of genetic diagnosis has not yet been realized, paradigms of clinical decision-making are changing. In fact, recent policy level changes to promote genetic counseling by certified genetics professionals (GP) such as genetic counselors and clinical geneticists, are occurring at both the payer and state level. However, there remain opportunities to develop policies within the United States to: 1) enhance the access to the limited workforce of GPs; 2) revise reimbursement schemes such that costs to deliver these services may be recouped by institutions with GPs; and 3) protect against the potential for discrimination based on genetic information. Although many of these issues predate advances in genomic technologies, they are exacerbated by them, with increasing access and awareness as costs of testing decrease. Consequently, evolving shifts in national policies poise GPs to serve as a hub of information and may be instrumental in facilitating new models to deliver genetics-based care through promoting academic-community partnerships and interfacing with non-GPs. As we acknowledge the potential for genomics to revolutionize medical practice, the expertise of GPs may be leveraged to facilitate incorporation of this information into mainstream medicine.

Comparison of Germline Genetic Testing Before and After a Medical Policy Covering Universal Testing Among Patients With Colorectal Cancer.

Importance: In 2020, some health insurance plans updated their medical policy to cover germline genetic testing for all patients diagnosed with colorectal cancer (CRC). Guidelines for universal tumor screening via microsatellite instability and/or immunohistochemistry (MSI/IHC) for mismatch repair protein expression for patients with CRC have been in place since 2009. Objectives: To examine whether uptake of MSI/IHC screening and germline genetic testing in patients with CRC has improved under these policies and to identify actionable findings and management implications for patients referred for germline genetic testing. Design, Setting, and Participants: The multicenter, retrospective cohort study comprised 2 analyses of patients 18 years or older who were diagnosed with CRC between January 1, 2017, and December 31, 2020. The first analysis used an insurance claims data set to examine use of MSI/IHC screening and germline genetic testing for patients diagnosed with CRC between 2017 and 2020 and treated with systemic therapy. The second comprised patients with CRC who had germline genetic testing performed in 2020 that was billed under a universal testing policy. Main Outcomes and Measures: Patient demographic characteristics, clinical information, and use of MSI/IHC screening and germline genetic testing were analyzed. Results: For 9066 patients with newly diagnosed CRC (mean [SD] age, 64.2 [12.7] years; 4964 [54.8%] male), administrative claims data indicated that MSI/IHC was performed in 6645 eligible patients (73.3%) during the study period, with 2288 (25.2%) not receiving MSI/IHC despite being eligible for coverage. Analysis of a second cohort of 55 595 patients with CRC diagnosed in 2020 and covered by insurance found that only 1675 (3.0%) received germline genetic testing. In a subset of patients for whom germline genetic testing results were available, 1 in 6 patients had pathogenic or likely pathogenic variants, with most of these patients having variants with established clinical actionability. Conclusions and Relevance: This nationwide cohort study found suboptimal rates of MSI/IHC screening and germline genetic testing uptake, resulting in clinically actionable genetic data being unavailable to patients diagnosed with CRC, despite universal eligibility. Effective strategies are required to address barriers to implementation of evidence-based universal testing policies that support precision treatment and optimal care management for patients with CRC.

Cancer risk assessment and genetics at the Helen F. Graham Cancer Center: model for personalized medicine and early intervention.

This article discusses cancer risk assessment, screening options, referral guidelines, and the experience of the Familial Risk Assessment Program at the Helen F. Graham Cancer Center. Two clinical situations are described that illustrate the impact of genetics in the multidisciplinary approach to managing cancer. Identifying risk level in patients will impact mortality in those at high risk, as well as psychosocial well-being in those at low risk.

A statewide survey of practitioners to assess knowledge and clinical practices regarding hereditary breast and ovarian cancer.

PURPOSE: This study describes practitioner knowledge and practices related to BRCA testing and management and explores how training may contribute to practice patterns. METHODS: A survey was mailed to all BRCA testing providers in Florida listed in a publicly available directory. Descriptive statistics characterized participants and their responses. RESULTS: Of the 87 respondents, most were community-based physicians or nurse practitioners. Regarding BRCA mutations, the majority (96%) recognized paternal inheritance and 61% accurately estimated mutation prevalence. For a 35-year-old unaffected BRCA mutation carrier, the majority followed national management guidelines. However, 65% also recommended breast ultrasonography. Fewer than 40% recognized the need for comprehensive rearrangement testing when BRACAnalysis(®) was negative in a woman at 30% risk. Finally, fewer than 15% recognized appropriate testing for a BRCA variant of uncertain significance. Responses appeared to be positively impacted by presence and type of cancer genetics training. CONCLUSIONS: In our sample of providers who order BRCA testing, knowledge gaps in BRCA prevalence estimates and appropriate screening, testing, and results interpretation were identified. Our data suggest the need to increase regulation and oversight of genetic testing services at a policy level, and are consistent with case reports that reveal liability risks when genetic testing is conducted without adequate knowledge and training.

Using adult learning theory concepts to address barriers to cancer genetic risk assessment in the African American community.

Utilization of cancer genetic risk assessment can be profoundly influenced by an individuals' knowledge of risk assessment, attitudes regarding illness and healthcare, and affective reactions derived from social norms. Race and ethnicity play a powerful role in the development of an individual's attitudes and should be considered when attempting to understand a person's openness to cancer genetic risk assessment (Lannin et al., 1998). Until recently, however, cancer screening and prevention programs have been primarily based on data from studies conducted with the Caucasian population, yielding data that are not fully applicable to the African American community. In the last several years, research findings regarding African American's knowledge, attitudes, and feelings about genetic counseling and testing have grown (Matthews et al., 2000; Singer et al., 2004; Thompson et al., 2003). However, to the authors' knowledge, these data have yet to be presented in a manner that both summarizes the barriers that African Americans have reported regarding cancer genetic risk assessment, while at the same time suggesting methods individual genetic counselors can utilize during community presentations to help address these barriers. This article will first summarize previous empirical findings regarding African Americans' knowledge, attitudes, and feelings about cancer genetic risk assessment. The article will then apply adult learning theory to those findings to provide genetic counselors with practical, theory based techniques to apply toward community based educational programs with African American groups.

A reciprocal translocation 46,XY,t(8;9)(p11.2;q13) in a bladder exstrophy patient disrupts CNTNAP3 and presents evidence of a pericentromeric duplication on chromosome 9.

A patient with sporadic bladder exstrophy and de novo apparently balanced chromosomal translocation 46,XY,t(8;9)(p11.2;q13) was analyzed by fluorescence in situ hybridization (FISH) and molecular methods. We were able to map both translocation breakpoints to single genomic clones. The chromosome 8p11.2 breakpoint was mapped to BAC clone RP4-547J18, predicted to contain several hypothetical genes. Characterization of the chromosome 9q13 breakpoint indicated a disruption in the 5' region of CNTNAP3 within BAC RP11-292B8. This observation suggests possible involvement of CNTNAP3 in the etiology of bladder exstrophy. Additionally, FISH analysis identified several genomic copies of CNTNAP3 on both sides of the chromosome 9 centromere flanking the polymorphic heterochromatin. Northern blot analysis of lymphoblast and bladder RNA confirmed CNTNAP3 transcripts in these tissues and did not show abnormal CNTNAP3 expression in the proband and two unrelated patients with bladder exstrophy. The identification of multiple copies of three BAC clones in the proband, his parents, and unrelated controls suggests that duplications of CNTNAP3 and the surrounding genomic region have occurred as a result of repeated events of unequal crossing over and pericentric inversions during chromosome 9 evolution.

Clinical and molecular characterization of the bladder exstrophy-epispadias complex: analysis of 232 families.

OBJECTIVE: To identify genetic and nongenetic factors contributing to the risk of bladder exstrophy-epispadias complex (BEEC). PATIENTS AND METHODS: In all, 285 families with BEEC were invited to participate in the study, and 232 of them were recruited. Epidemiological information was obtained from 151 of the consenting families, with a detailed clinical genetic examination of 94 probands. In all, 440 DNA samples were collected from 163 families for molecular analysis. RESULTS: Most of the cases were sporadic and had no family history of BEEC. Among patients, 95% were Caucasian, and males were more common in both the epispadias group (M/F, 2.2, 29 patients) and the classic bladder-exstrophy group (M/F 1.8, 164), but in the cloacal exstrophy group the sex ratio was close to unity (1.1, 15). There was a statistically significant association with advanced parental age (P < 0.001). Birth weight, gestational age and maternal reproductive history did not appear to be significantly different from those in the general population. Information on exposures to tobacco, alcohol and drugs was collected but none appeared to act as a risk factor. Karyotype analysis on 37 cases detected two chromosomal abnormalities, i.e. 46XY t(8;9)(p11.2; q13) and 47XYY. Molecular analysis of the HLXB9 gene, which causes Currarino syndrome, did not detect mutations in the blood or bladder DNA of 10 patients with bladder or cloacal exstrophy. CONCLUSIONS: BEEC most commonly occurs as an isolated sporadic birth defect with a recurrence risk of << 1%. There was no evidence of a single-gene effect or common environmental factor in this study population. In addition to race and advanced parental age, birth order may be a risk factor for BEEC. We suggest somatic mutations in a gene(s) within the pathway regulating bladder development may be the cause of BEEC.