Intestinal Carcinoid Tumours in a Father and Daughter

Familial cases of carcinoid tumours that are not associated with any known syndrome or disease are extremely rare. All cases reported in the world literature have involved carcinoid tumours of the gastrointestinal tract. Two cases of carcinoid tumours of the small intestine in a father and daughter are presented. Laboratory analyses did not support the hypothesis that the occurrence of carcinoid tumours in this family is a variant of the multiple endocrine neoplasia type 1 syndrome. A review of the literature on familial occurrence of intestinal carcinoid tumours in the absence of any other known carcinoid tumour-predisposing genetic syndrome is provided

Enhancing Cancer Care of Rural Dwellers through Telehealth and Engagement (ENCORE): Protocol to Evaluate Effectiveness of a Multi-Level Telehealth-Based Intervention to Improve Rural Cancer Care Delivery

BACKGROUND: Despite lower cancer incidence rates, cancer mortality is higher among rural compared to urban dwellers. Patient, provider, and institutional level factors contribute to these disparities. The overarching objective of this study is to leverage the multidisciplinary, multispecialty oncology team from an academic cancer center in order to provide comprehensive cancer care at both the patient and provider levels in rural healthcare centers. Our specific aims are to: 1) evaluate the clinical effectiveness of a multi-level telehealth-based intervention consisting of provider access to molecular tumor board expertise along with patient access to a supportive care intervention to improve cancer care delivery; and 2) identify the facilitators and barriers to future larger scale dissemination and implementation of the multi-level intervention. METHODS: Coordinated by a National Cancer Institute-designated comprehensive cancer center, this study will include providers and patients across several clinics in two large healthcare systems serving rural communities. Using a telehealth-based molecular tumor board, sequencing results are reviewed, predictive and prognostic markers are discussed, and treatment plans are formulated between expert oncologists and rural providers. Simultaneously, the rural patients will be randomized to receive an evidence-based 6-week self-management supportive care program, Cancer Thriving and Surviving, versus an education attention control. Primary outcomes will be provider uptake of the molecular tumor board recommendation and patient treatment adherence. A mixed methods approach guided by the Consolidated Framework for Implementation Research that combines qualitative key informant interviews and quantitative surveys will be collected from both the patient and provider in order to identify facilitators and barriers to implementing the multi-level intervention. DISCUSSION: The proposed study will leverage information technology-enabled, team-based care delivery models in order to deliver comprehensive, coordinated, and high-quality cancer care to rural and/or underserved populations. Simultaneous attention to institutional, provider, and patient level barriers to quality care will afford the opportunity for us to broadly share oncology expertise and develop dissemination and implementation strategies that will enhance the cancer care delivered to patients residing within underserved rural communities. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04758338 . Registered 17 February 2021 - Retrospectively registered, http://www.clinicaltrials.gov/

Complex cytogenetic rearrangements at the DURS1 locus in syndromic Duane retraction syndrome

Key Clinical Message A patient with syndromic Duane retraction syndrome harbors a chromosome 811.1q13.2 inversion and 8p11.1-q12.3 marker chromosome containing subregions with differing mosaicism and allele frequencies. This case highlights the potential requirement for multiple genetic methods to gain insight into genotype–phenotype correlation, and ultimately into molecular mechanisms that underlie human disease

MRI Surveillance and Breast Cancer Mortality in Women With <i>BRCA1</i> and <i>BRCA2</i> Sequence Variations

Importance: Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. Objective: To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Design, Setting, and Participants: Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Exposures: Entrance into an MRI surveillance program. Main Outcomes and Measures: Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. Results: A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P  Conclusion and Relevance: Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.</p

Using Genome and Transcriptome Data From African-Ancestry Female Participants To Identify Putative Breast Cancer Susceptibility Genes

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3\u27 UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P \u3c 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P \u3c 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations

Hereditary Cancer: Example of a Public Health Approach to Ensure Population Health Benefits of Genetic Medicine

This article introduces the identification, prevention, and treatment of hereditary cancer as an important public health concern. Hereditary cancer research and educational outreach activities are used to illustrate how public health functions can help to achieve health benefits of genetic and genomic medicine. First, we evaluate genetic service delivery through triangulating patient and provider survey results which reveal variability among providers in hereditary cancer knowledge and genetic service provision. Second, we describe efforts we have made to assure competency among healthcare providers and to inform, educate and empower patients with regard to the rapidly evolving field of genomics and hereditary cancer. Lastly, key policy-issues raised by our experiences are discussed in the context of how they may help us to more effectively translate future genomic technologies into practice in order to attain population health benefits from genetic and genomic medicine

Development of a Brochure for Increasing Awareness of Inherited Breast Cancer in Black Women

Low levels of awareness about hereditary breast cancer and ovarian cancer and underutilization of genetic services combined with the high incidence of early onset breast cancer in the black community underscore the urgent need to provide information about hereditary breast and ovarian cancer to black women. The primary goal of the present study was to develop a culturally targeted brochure designed to increase awareness about inherited breast cancer among black women using the principles of Learner Verification. Three focus groups were conducted with black women, including those with or without a history of breast cancer (n = 46), to evaluate the brochure. Data were analyzed through hand coding using a simple classification system placing participants\u27 responses in the predetermined Learner Verification categories. On the basis of the feedback obtained, the brochure has been modified to improve cultural-targeting, relevance, and clarity and has been made available for dissemination. Our study illustrates the importance of obtaining feedback from the target audience when developing a culturally targeted informational brochure for black women. Further, the complexity of our subject matter (i.e., inherited breast and ovarian cancer) underscores the importance of using inviting visuals and personal vignettes, while maintaining a simple and clear message

Development of a Brochure for Increasing Awareness of Inherited Breast Cancer in Black Women

Low levels of awareness about hereditary breast cancer and ovarian cancer and underutilization of genetic services combined with the high incidence of early onset breast cancer in the black community underscore the urgent need to provide information about hereditary breast and ovarian cancer to black women. The primary goal of the present study was to develop a culturally targeted brochure designed to increase awareness about inherited breast cancer among black women using the principles of Learner Verification. Three focus groups were conducted with black women, including those with or without a history of breast cancer (n = 46), to evaluate the brochure. Data were analyzed through hand coding using a simple classification system placing participants\u27 responses in the predetermined Learner Verification categories. On the basis of the feedback obtained, the brochure has been modified to improve cultural-targeting, relevance, and clarity and has been made available for dissemination. Our study illustrates the importance of obtaining feedback from the target audience when developing a culturally targeted informational brochure for black women. Further, the complexity of our subject matter (i.e., inherited breast and ovarian cancer) underscores the importance of using inviting visuals and personal vignettes, while maintaining a simple and clear message

Intestinal Carcinoid Tumours in a Father and Daughter

Familial cases of carcinoid tumours that are not associated with any known syndrome or disease are extremely rare. All cases reported in the world literature have involved carcinoid tumours of the gastrointestinal tract. Two cases of carcinoid tumours of the small intestine in a father and daughter are presented. Laboratory analyses did not support the hypothesis that the occurrence of carcinoid tumours in this family is a variant of the multiple endocrine neoplasia type 1 syndrome. A review of the literature on familial occurrence of intestinal carcinoid tumours in the absence of any other known carcinoid tumour-predisposing genetic syndrome is provided