Hereditary Risk Research Articles

Validation of a guidelines-based digital tool to assess the need for germline cancer genetic testing

BackgroundEfficient and scalable solutions are needed to identify patients who qualify for germline cancer genetic testing. We evaluated the clinical validity of a brief, patient-administered hereditary cancer risk assessment digital tool programmed to assess if patients meet criteria for germline genetic testing, based on personal and family history, and in line with national guidelines.MethodsWe applied the tool to cases seen in a nationwide telehealth genetic counseling practice. Validity of the tool was evaluated by comparing the tool’s assessment to that of the genetic counselor who saw the patient. Patients’ histories were extracted from genetic counselor-collected pedigrees and input into the tool by the research team to model how a patient would complete the tool. We also validated the tool’s assessment of which specific aspects of the personal and family history met criteria for genetic testing. Descriptive statistics were used.ResultsOf the 152 cases (80% female, mean age 52.3), 56% had a personal history of cancer and 66% met genetic testing criteria. The tool and genetic counselor agreed in 96% of cases. Most disagreements (4/6; 67%) occurred because the genetic counselor’s assessment relied on details the tool was not programmed to collect since patients typically don’t have access to the relevant information (pathology details, risk models). We also found complete agreement between the tool and research team on which specific aspects of the patient’s history met criteria for genetic testing.ConclusionWe observed a high level of agreement with genetic counselor assessments, affirming the tool’s clinical validity in identifying individuals for hereditary cancer predisposition testing and its potential for increasing access to hereditary cancer risk assessment.

Using Social Robots and AI to Perform Genetic Risk Assessment for Cancer

Genetic risk assessment (GRA) and genetic counseling have become integral to optimal patient care for patients with cancer. At present, there is a limited number of qualified healthcare providers who provide this service. To assist professionals in the GRA process, we have combined social robotics and retrieval-augmented generative artificial intelligence (RAG AI) to provide education related to hereditary cancer to be included in GRA sessions for individuals at risk. This GRA application pushes the boundary on previously available chatbots and AI systems by creating a novel and interactive experience enhanced by professionally verified information. In the future, we seek to improve the app as it is and obtain feedback from both GRA professionals and potential end-users that will be used to enhance the system and provide customized risk assessment. Overall, our GRA system takes the next step towards informing patients of their hereditary cancer risk and pertinent care options.

Communicatively constructing resilience: Exploring family resilience in the experience of hereditary cancer

AbstractObjectiveThe goal was to explore how families communicate to cope with hereditary cancer conditions and identify factors that may enhance resilience and recommended decision‐making.BackgroundFamilies with Hereditary Breast and Ovarian Cancer syndrome (HBOC), Lynch syndrome (LS), and Li‐Fraumeni syndrome (LFS) have an increased lifetime risk of developing cancer. We use the communication theory of resilience (CTR) to examine how families engage in resilience and make health decisions about hereditary cancer risks over time.MethodWe conducted 42 dyadic interviews with families with HBOC, LS, and LFS. Themes emerged through qualitative analysis for each of the resilience processes outlined by CTR (crafting normalcy, communication networks, identity anchors, alternative logics, and foregrounding productive action while legitimizing negative feelings), illustrating how family members manage stressors associated with hereditary cancer over time.ResultsParticipants described enacting each of the five CTR processes to manage the acute and chronic stressors associated with hereditary cancer. We described themes that emerged within each of the five resilience processes.ConclusionFindings demonstrate the ways in which families managing hereditary cancer risks enact resilience processes and how these processes may have a complex relationship to coping and medical decision‐making.ImplicationsFindings demonstrate areas for intervention to support familial resilience.

Autism: A review

Reduced eye contact, facial expressions, and body movements during the first three years of life are among the social behaviors and nonverbal interactions that define autism spectrum disorder (ASD), a collection of neurodevelopmental diseases. It is generally accepted that this condition is a multifactorial disorder resulting from the combination of both hereditary and non-genetic risk factors. It is not a single disorder. Studies on the genetics of ASD have found mutations that disrupt normal neurodevelopment from infancy through childhood. Axon mobility and synaptogenesis have been linked to these gene complexes. Advances in neuroimaging research have yielded numerous significant insights into the pathological alterations that take place in the brains of individuals with ASD while they are living their lives. Numerous neuropathological and neuroimaging studies have demonstrated the significance of the amygdala, a key component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD. The nucleus accumbens is seen as another important structure associated with the social reward response in ASD, in addition to the amygdala. While behavioral and educational interventions have traditionally been the cornerstones of ASD care, pharmaceutical and interventional therapies have also demonstrated some promise in ASD patients. Additionally, a small number of individuals have reportedly improved following deep brain stimulation, one of the interventional treatments.

Colorectal cancer and associated genetic, lifestyle, cigarette, nargileh-hookah use and alcohol consumption risk factors: a comprehensive case-control study.

This study aimed to investigate the causes and risk factors of colorectal cancer (CRC) in a Turkish population, focusing on various modifiable and non-modifiable risk factors. A hospital-based case-control design was employed to compare individuals with CRC (cases) to individuals without CRC (controls). Male and female participants were recruited from the surgery, internal medicine, and out-patient departments. The study encompassed socio-demographic data, clinical information, radiological diagnoses, and biochemical measurements. Univariable and multivariable logistic regressions were used to determine associated risk factors of CRC. The study included 704 individuals with CRC and 704 controls. Significant socio-demographic disparities were observed between the groups, with over 30% of the cases having lower levels of education and income compared to the controls. Lifestyle factors such as obesity, higher rates of smoking (cigarettes and hookah) and alcohol consumption were more prevalent among cases than controls. Further significant associations were identified with intestinal inflammation, obesity, processed food consumption, and symptoms such as abdominal pain, cramps, diarrhea, constipation, blood in stool, bloating, irritable bowel syndrome, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Diet analysis revealed that individuals with CRC consumed more red meat, processed and fast foods along with less pulses and vegetables. Genetic predispositions and exposure to chemicals also correlated strongly with increased CRC risk. Multivariable regression analysis identified, nausea/vomiting, constipation, intestinal disease, genetics factor, hookah-nargileh use, history of any cancer, family history of bowel cancer, constipation, cigarette smoking, stress, milk-yogurt consumption, obesity and red meat consumption as significant determinants for CRC. CRC risk is influenced by dietary, lifestyle, and genetic factors. Awareness of hereditary risk and participation in screening are crucial. Lifestyle changes, such as avoiding smoking, hookah, and alcohol use, and adopting a healthy diet, are essential for prevention.

Genetic Predisposition for Gynecologic Cancers.

Hereditary cancer syndromes (HCS) are responsible for up to 10% of all cancers. At present, the majority of cancer susceptibility testing is initiated after a cancer diagnosis. There exists a significant opportunity for primary care providers including general obstetrician-gynecologists to engage in hereditary cancer risk assessment through adequate family history evaluation, initiation of genetic testing, and following the recommendations of national organizations. Identifying hereditary cancer genes may prompt primary prevention efforts such as enhanced screening, prevention, or personalized care strategies. We will review the literature regarding the approach and assessment of the most common gynecologic HCS.

Implementation of hereditary cancer risk assessment in primary care: Intervention strategies and proximal outcomes.

279 Background: Family history-based risk assessment for hereditary breast and ovarian cancer and Lynch syndrome is guideline recommended and has strong evidence supporting its implementation into clinical practice, especially primary care. Yet, adoption has been impeded by limited awareness of genetic evaluation guidelines among primary care providers (PCPs), time constraints in screening during appointments, and limited resources for follow-up within primary care. To close this gap, we implemented a hereditary cancer risk assessment program that addresses these barriers and evaluated proximal implementation outcomes. Methods: We used intervention mapping for adaptation (IM-Adapt), a modified version of Intervention Mapping to guide the adaptation and implementation of the evidence-based 7-question family history screening (FHS-7) at a primary care clinic within an academic medical center. FHS-7 was adapted for administration via electronic patient portal prior to PCP visit or in-person at PCP visit. All clinic patients were offered screening and follow-up genetic counseling and testing per guidelines. Administrative, programmatic, and electronic medical record data were analyzed for program evaluation. Results: Between February 2023 and March 2024, 4,540 primary care patients were offered hereditary cancer risk assessment and 3,497 (77%) completed screening. Patient portals were used to complete screening more frequently than in-person at the clinic (86.6% vs 13.4%). Among patients with qualifying family history of cancer (n=1,267, 36%), 1,117 (88%) were eligible for navigation as they completed their primary care appointment and did not undergo genetic counseling within the last 5 years. Of the eligible patients, 62% were successfully contacted by a navigator and offered genetic counseling. Program implementation was facilitated by key personnel (clinical champion, informatics staff, genetic patient navigator) and adaptations to fit the implementation setting (adapting FHS7 for patient self-report rather than administration by PCP, patient population with high patient-portal adoption rate and in-house genetic service resources). Conclusions: We demonstrate the feasibility of hereditary cancer risk assessment within primary care and describe actionable aspects of the implementation context that influence screening uptake that can be incorporated into the design of future implementation for maximum impact. Findings advance the state of science in identification of unaffected individuals with inherited cancer susceptibility and genetic service delivery.

Assessing capacity for hereditary cancer risk assessment in metro Chicago.

307 Background: Since 2005, the United States Preventive Services Task Force (USPSTF) recommends that primary care (PC) clinicians identify and refer adults with a high-risk cancer family history to cancer genetic services (CGS), yet hereditary cancer risk assessment (HCRA) continues to be underutilized in PC. A population-based approach to HCRA in PC settings can expand access to cancer prevention and early detection to vulnerable populations and reduce disparities in cancer outcomes. The Chicago Cancer Screening and Testing Access Coalition (CCSTAC) is developing strategies to integrate HCRA in PC settings. We conducted an environmental scan to assess current capacity to deliver 1) HRCA in Federally Qualified Health Centers (FQHCs) and 2) follow-up CGS for high risk patients. Methods: In 2023, we administered two surveys to assess HCRA practices in Metro Chicago. We invited 22 FQHCs to complete a 21-item survey of current practices, readiness to implement, and barriers to HCRA. We also invited 21 CGS sites to complete a 25-item survey to understand staffing, utilization, referral patterns, and barriers to access. Surveys were administered electronically via Qualtrics. We conducted a descriptive analysis of survey data. Results: Twenty FQHCs (91%) completed the survey on HCRA in PC; 85% reported familiarity with USPSTF guidelines for HCRA. The majority (75%) reported no plans to implement HCRA. Clinic workflow, paucity of follow-up resources, cost, lack of provider knowledge, and absence of HCRA as a mandatory performance measure were cited as the most significant barriers to implementation. Genetic counselors (GCs) from 19 CGS hospital-based sites (90%) completed the survey on availability of genetic services. CGS were most often located in a cancer center (47%); no CGS were located in PC. Most referrals originated from oncology, surgery, or gastroenterology, with the lowest rate of referrals from community-based PC. Nearly half of CGS clinics (47%) reported capacity for at least a small increase in patient volume. Wait-time at the majority of CGS clinics was less than a month. GCs cited patient logistics (e.g. transportation, time off work), lack of referral information from providers, and systemic racism as significant barriers in patient access to CGS. Conclusions: After almost 20 years of evidence-based guidelines, use of HCRA is still very limited in the community-based PC setting. Our findings point to a need to bridge the gap between hospital-based CGS and FQHCs to ensure patients in vulnerable communities have access to guideline-concordant cancer prevention and screening strategies. Based on these findings, CCSTAC is designing strategies to integrate HCRA in primary care at FQHCs focused on provider education, well-designed clinic workflows, connections with existing CGS, and advocacy to align UDS and HEDIS measures with USPSTF guidelines.

Exploring barriers to completing referral appointments for cancer genetic services in a rural state.

83 Background: Genetic counseling and testing promotes awareness and management of hereditary cancer risk. Barriers exist to accessing cancer genetic services, particularly among those with healthcare disparities, i.e., those facing geographic and socioeconomic barriers. These barriers impact not only the ability to obtain a referral but also whether the initial appointment is scheduled and completed. This study explored referrals and what factors were associated with whether appointments were successfully completed in a predominantly rural state (Maine). Methods: Medical records were reviewed for patients referred to the state’s largest health system-based cancer genetic program from 2017 through 2023. We evaluated factors that may be associated with referral completion within 90 days. These included: year of referral, patient factors, clinical factors, and health system factors. Associations were examined using univariate logistic regression models. Results: A total of 11,643 referrals were placed and examined over the period studied. Despite a steady increase in the number of referrals, the percent of referrals that were successfully completed decreased over time (54.04% in 2017 to 51.06% in 2023). Patients with older age and whose primary language was identified as English had greater likelihood of completing the referral (OR = 1.01; p < 0.001 and OR = 3.37; p < 0.001, respectively). Patients living in isolated rural areas and those without insurance were less likely to complete the referral (OR =0.84 and OR 0.61; p < 0.001, respectively). Patients with a cancer diagnosis were almost three times more likely to complete the referral (OR = 2.93; p < 0.001). Referrals scheduled as telemedicine appointments were less likely to be completed (OR =0.63; p < 0.001); and referrals coming from providers within the health system were twice as likely to be completed (OR = 2.15; p < 0.001). Conclusions: Successful completion of referral appointments to cancer genetic services varied by several important patient, clinical, and health system factors. Further multivariate analyses will be conducted. Strategies including language translation, educational materials, and financial assistance might boost the completion rate for structurally vulnerable patients. Systems aimed at streamlining the scheduling process are needed to support all individuals in accessing cancer genetic services, with a focus on those with healthcare disparities.

“I Didn't Have to Worry about It”: Patient and Family Experiences with Health System Involvement in Notifying Relatives of Genetic Test Results

Introduction: In the USA, patients who undergo genetic testing for hereditary cancer risk are responsible for informing relatives about their genetic test results, but many relatives never find out they might be at risk. A health system-mediated relative notification program might help fill this gap, but questions remain about the acceptability of this approach. Methods: We analyzed qualitative data from a single-arm, nonrandomized, mixed-methods study to understand how patients and families experienced a new health system-mediated relative notification program. We invited all study participants to participate in semi-structured telephone interviews at 6–8 weeks after return of genetic test results. We used a template analysis approach to thematically analyze interview transcripts. Results: We interviewed 32 participants, including 17 probands and 15 relatives. Relatives reported positive experiences with the notification program, noting they felt in control of decisions and appreciated genetic counselor involvement in communicating the proband’s test results. Benefits of direct contact included reduced burden for probands, increased family discussions about health, and notification of relatives who otherwise would not have learned results. No participants reported adverse effects from the program. Conclusion: Overall, the relative notification program was acceptable to participants and supported probands in reaching at-risk relatives who otherwise might not have been notified. These findings could inform the implementation of future genetic risk family notification programs with the potential to improve uptake of cascade testing and advance cancer prevention and early detection efforts.

Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis.

PALB2 is a tumor suppressor gene. Heterozygous germline pathogenic variants of PALB2 significantly increase the lifetime risk of breast cancer and moderately increase the risk of ovarian and pancreatic cancers. This study analyzed the estimated prevalence of PALB2 variants globally, focusing on East Asian and Korean populations, where limited data were previously available. We examined 125,748 exomes from the Genome Aggregation Database (gnomAD), including 9197 East Asians, and additional data from 5305 individuals in the Korean Variant Archive and 1722 in the Korean Reference Genome Database. All PALB2 variants were interpreted according to guidelines from the American College of Medical Genetics and Genomics and the Clinical Genome Resource. The global prevalence of PALB2 variants was 0.18%, with the highest prevalence in Finnish populations (0.41%) and the lowest in Ashkenazi Jewish populations (0.04%). East Asians had a prevalence of 0.09%. By combining data from Korean genome databases and gnomAD totaling 8936 individuals, the overall prevalence of PALB2 variants in the Korean population was determined to be 0.13%. This study is the first comprehensive investigation of PALB2 variant prevalence in East Asians and Koreans using gnomAD and Korean genome databases. These findings provide essential reference data for future research and highlight the importance of region-specific genetic studies that will inform genetic counseling and hereditary cancer risk management.

Hereditary and clinical insights into paraganglioma and pheochromocytoma.

Approximately 30-40% of paragangliomas (PGLs) and pheochromocytomas (PCCs) harbor an underlying hereditary cause. Early identification of at-risk individuals is imperative given the early onset, aggressiveness of tumors, and other tumor/cancer risks associated with hereditary PGLs/PCCs. This study analyzes the clinical presentations and genetic histories of patients with PGL/PCC and/or hereditary risk to contribute to the expanding knowledge in this rare population. A retrospective chart review identified two cohorts of patients seen in cancer genetics clinics at an academic medical center and a safety-net hospital between August 2016 and December 2022. Cohort 1 consisted of patients with likely pathogenic variants (LPVs)/pathogenic variants (PVs) in hereditary PGL/PCC predisposition genes. Cohort 2 consisted of patients with a personal history of a PGL/PCC. Demographics, personal/family history, and genetic testing outcomes were analyzed. A total of 560 patients met the study criteria (Cohort 1, n = 364; Cohort 2, n = 269). In Cohort 1, 77 (21.1%) patients had an incidental LPV/PV in a PGL/PCC gene. Nearly half (n = 36, 46.8%) were in SDHx genes, with a majority in SDHA (n = 21). In Cohort 2, 86 patients tested positive for 87 LPV/PV in a hereditary cancer predisposition gene. The SDHx genes were most likely to have an LPV/PV identified (SDHB n = 24, SDHD n = 23). Multigene panels identify patients at risk for hereditary PGL/PCC, many of whom are incidentally found. While SDHA LPV/PVs were the most frequent incidental finding, they were less common in patients with PGL/PCC, indicating the need for longitudinal studies to better understand the prevalence and penetrance of these tumors.

Abstract A084: Journey to understanding indigenous peoples engagement in cancer genomic research

Abstract Introduction: Tribal Nations across the Southwest have striking disparities in cancer incidence and mortality. Compounded by disproportionately low rates of cancer screening and limited access to healthcare, Native Americans are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer when compared to any other racial and ethnic group in the United States. At the University of New Mexico Comprehensive Cancer Center, the Participant Engagement Cancer Genomic Sequencing (PE-CGS) Center is developing culturally appropriate materials and strategies to enhance the engagement and recruitment of Native Americans into genomic research. This effort aims to determine participant knowledges, attitudes, cultural beliefs, and communication preferences regarding clinical genomics testing. Ultimately, targeting improvement of cancer outcomes in Southwestern Tribal communities. Cultural adaptations are crucial with regards to biospecimen collection, storage, and usage, due to historical mistrust of research among Native communities. (i.e., Havasupai Tribe v. the Arizona Board of Regents). A Tribal Advisory Committee, consisting of Tribal leaders, Native physicians, and patient advocates oversee all aspects of the research study. The goal is to identify appropriate optimized health literacy strategies for engaging Native peoples in cancer genomic research. Methods: The team conducted semi-structured discussions with participants to understand their perspectives on motivations to join, cultural safety components, and effectiveness of engagement strategies. With participant consent, the discussions were recorded and transcribed. Analysis included the transcripts and notes taken by the interviewer and followed Grounded Theory principles. All transcripts and notes followed line-by-line analysis by three of the authors (JS, JR and TG) who met regularly to identify and discuss emergent themes. Results: As of May 31, 2024, the PE-CGS study has enrolled 112 participants and completed 39 discussions. Participants emphasized altruistic motives tied to family and community, echoing traditional values, in their decision to participate in the study. This notion emerged during interactions with Native team members, where comfort stemmed from shared experiences (healthcare system, barriers), use of Native language, and adherence to Native social norms. Additional considerations included present autonomy throughout various stages of the study (sample use, data sharing, discussions). Return of genetic testing results improved understanding of treatment options, hereditary risk, and health literacy. Conclusion: Feedback highlights the importance of aligning cultural beliefs with Western medicine through a strengths-based approach. The findings will inform improvements in respectful engagement, communication, information exchange, and recruitment processes with Native American cancer patients and cancer survivors to genomic testing studies. Citation Format: Jessica Sanchez, Koby Blackwater, Joseph Rodman, Tamar Ginossar, Andrew Sussman, Shiraz Mishra, Cindy Blair, Mallery Quetawki, Debra MacKenzie, V. Shane Pankratz, Ursa Brown-Glaberman, Jeffery Trent, Cheryl Willman. Journey to understanding indigenous peoples engagement in cancer genomic research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A084.

Abstract C125: Improving access to genetic counseling and testing for underserved populations through telehealth

Abstract Introduction: A lack of access to genetic counseling for hereditary cancer risk in rural and underserved areas is well-documented and can exacerbate disparities in cancer risk reduction and early detection. Telehealth has the potential to bridge this gap, providing remote access to specialized care. The COVID-19 pandemic accelerated telehealth availability, allowing estimation of the causal effects of shifting to a model of virtual care delivery for genetic counseling services. Methods: The Stanford Cancer Genetic Counseling Clinic provided solely in-person care at two clinical sites (Palo Alto and San Jose, CA) until March 2020, and solely virtual care from April 2020 onward. We performed a regression discontinuity design, allowing outcomes comparison before and after the threshold of early 2020, to evaluate the impact of telehealth genetic counseling on access to care for patients living in areas of higher deprivation. The assignment variable (the exposure measured before versus after the threshold) was the three-month period during which the patients were seen, with the March-May 2020 quarter excluded because of disruption of care during the early COVID-19 pandemic. The primary endpoint was proportion of patients whose primary residence zip code had a state area deprivation index of at least 4. Secondary endpoints included driving distance to the primary clinic location in Palo Alto, CA, insurance type, race/ethnicity, and primary language. Results: The study included N=5,957 patients seen in the Stanford Cancer Genetics Program between January 2017 and February 2020, and N=9,469 patients seen between June 2020 and April 2024. The regression discontinuity analysis revealed a significant discontinuity at the threshold for telehealth in access for patients living in areas of higher deprivation, who accounted for 22% of patients seen just prior to telehealth implementation and 27% just after telehealth implementation, a proportional increase of 21% (p=0.006). Mean driving distance to Palo Alto, CA also increased, from 49 minutes just prior to the threshold to 56 minutes just after (p=0.003). There were no significant differences in insurance type, race/ethnicity, or primary language across the threshold. Conclusion: The implementation of telehealth services at the Stanford Cancer Genetic Counseling Clinic significantly improved access to genetic counseling for patients from areas with higher deprivation, as evidenced by a 21% increase in the proportion of such patients among those seen. These results quantify the effectiveness of telehealth in reducing geographical and socioeconomic barriers to specialized genetic counseling and testing services. Citation Format: Jennifer L. Caswell-Jin, Hao Tang, Mina Satoyoshi, Kerry Kingham, Allison W. Kurian. Improving access to genetic counseling and testing for underserved populations through telehealth [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C125.

Factors Impacting Intent to Share Multigenic Cancer Testing Results in a Community Hospital Setting.

Multi-gene, multi-cancer, hereditary cancer risk screenings may be useful in cancer prevention and treatment, not only for cancer patients but also for patients' family members. If genetic cancer screening is to have the widest possible benefit, it must be extended into diverse cancer care settings that serve diverse patient communities, providing cancer patients and their relatives with individualized cancer risk evaluations. Little research, to date, has examined the impact of extending multigenic cancer screening into diverse settings. Without empirical data characterizing the support needs of cancer patients and their family members, we may not adequately satisfy the needs of all patients and risk exacerbating existing disparities in cancer care and outcomes. We examined patient perspectives on the sharing of genetic results with at-risk family members by surveying a racially diverse sample of cancer patients receiving a multi-gene, multi-cancer risk screen in a community hospital setting. In a survey of 230 cancer patients, we found that intent to share results with family members was high but varied across family member types. More respondents planned to disclose results to at least one sister (82.5%) compared to at least one brother (73.1%). Over one-fourth of participants (27.4%) were either uncertain about sharing or intended to withhold their genomic screening results from at least one at-risk family member eligible for cascade testing. Participants were more likely to withhold their results from a sibling than from a child. Furthermore, intent to share across all family member types was lower if probands failed to identify at least one benefit to sharing. Understanding factors associated with decisions to share results with at-risk relatives in diverse patient populations can help clinicians support cascade genetic cancer screenings in diverse communities and settings.

The “Latines Lideres En Salud (LaLiSa)” study: Rationale and design

BackgroundLatines suffer from breast cancer (BC), due to elevated biological and social determinants of health (SDOH) risks. This study compares the effects of different strategies on uptake of cancer genetic services, specifically hereditary cancer risk assessment, genetic counseling, and genetic testing, and risk-based BC care. Design/methodsIn Chicago, Illinois, Aim 1 participants are recruited from a federally qualified health center (FQHC) and community venues. For Aim 1, eligible participants: (1) are female; (2) are Latine; (3) are 30+ years old; (4) have personal or family history of BC or cancers with shared hereditary mutations; (5) have at least one SDOH risk; and (6) have not received any cancer genetic services. Participants are randomly assigned to different study arms. Both arms include phone-based sessions, FQHC-based navigation for SDOH, and low- or no-cost cancer genetic services. The educate sessions focus on risk assessment and prevention. The empower sessions focus on risk assessment and equip participants with the skills to share information about FQHC-based cancer genetic services. For Aim 2, eligible participants are: (1) female; (2) network members of Aim 1 participants; and (3) eligible for BC screening based on guidelines recommended by the American Cancer Society (ACS). Primary outcomes include uptake of any cancer genetic services. Analyses will also explore intervention differences by neighborhood context. DiscussionThis is one of the first trials focused on Latines' participation in cancer genetic services and risk-based BC care within the context of SDOH - which has major implications for equity in precision cancer prevention.

Premarital Screening Uncovers Alarming Health Risks in Iraq

Background: Premarital screening programs, implemented globally since the 1970s, aim to improve reproductive health outcomes by identifying potential genetic and infectious risks before marriage. Specific Background: In July 2013, the Thi-Qar Governorate in Iraq introduced a premarital screening program to enhance health outcomes for pregnant women and their offspring. However, regional data on the efficacy and impact of such programs remain limited. Knowledge Gap: The prevalence and distribution of blood disorders and infectious diseases among couples in this region, and their implications for public health, have not been extensively documented. Aims: This study evaluates the pathophysiological status of couples undergoing premarital screening in Nasiriyah, Iraq, focusing on the prevalence of blood disorders and infectious diseases. Results: Data from 14,190 individuals (7095 couples) collected from January to December 2023 revealed significant health concerns: 34.40% had hemoglobin levels below 12 gm/dl, and notable percentages carried thalassemia and sickle cell anemia genes. Gender-specific analysis showed that all males tested positive for HIV, while significant proportions of females tested positive for HCV and T. palladium. No significant differences were found in the ABO blood system. Novelty: This study provides comprehensive, region-specific data on premarital screening outcomes in Iraq, highlighting significant disparities in disease prevalence between sexes and compared to other regions. Implications: The findings underscore the importance of enhancing premarital screening programs and integrating educational and preventive measures. Future research should include longitudinal studies to assess the long-term impact of these screenings and explore the benefits of incorporating genetic counseling to further mitigate hereditary and infectious risks. Highlights: High prevalence of blood disorders and infections in couples. Gender differences: all males positive for HIV, significant female infections. Need for improved education and prevention measures. Keywords: Premarital Screening, Hemoglobinopathies, Infectious Diseases, Nasiriyah, Iraq

IKNOW—Supporting the counseling of women with hereditary risk of breast and ovarian cancer with digital technologies: A randomized controlled trial

PurposeWe developed the online-based counseling tool iKNOW for women with a pathogenic germline variant in BRCA1/2 to improve risk understanding and quality of life. MethodsWith a randomized controlled trial, we investigated the efficacy of iKNOW with regard to risk understanding (primary endpoint), quality of life, risk perception, and anxiety (secondary endpoints). Self-report questionnaires were administered to N = 217 women with a pathogenic variant in BRCA1/2 before counseling (T0), immediately after (T1), 4 weeks after (T2), and 6 months after (T3). ResultDeviations between self-assessed and calculated cancer risks tended to be smaller in the intervention group than in the control group but no longer significantly after adjustment for multiple testing. In the intervention group, the proportion of women with a correct understanding of breast cancer risk at T3 was higher (30.7% vs 14.7%; P = .032). There were no differences in secondary endpoints. ConclusioniKNOW tends to positively influence the understanding of familial cancer risk. At the same time, it does not negatively influence any of the secondary endpoints. However, converging evidence suggests that iKNOW seems to affect the quality of counseling processes and can thus be used as a paradigm for reinventing the notion of efficient, digital care.

Pediatric Cancer Screening in Hereditary Gastrointestinal Cancer Risk Syndromes: An Update from the AACR Childhood Cancer Predisposition Working Group.

Gastrointestinal (GI) polyposis and cancer in pediatric patients is frequently due to an underlying hereditary cancer risk syndrome requiring ongoing cancer screening. Identification of at-risk patients through family history, clinical features of a syndrome, or symptom onset ensures appropriate cancer risk assessment and management in childhood and beyond. In this 2024 perspective, we outline updates to the hereditary GI cancer screening guidelines first published by the American Association of Cancer Research Pediatric Cancer Predisposition Workshop in 2017. These guidelines consider existing recommendations by pediatric and adult gastroenterology consortia to ensure alignment with gastroenterology practices in managing polyposis conditions. We specifically address the recommendations for pediatric screening in familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Further, we emphasize the importance of multidisciplinary care and partnership with gastroenterology, as it is crucial in management of children and families with these conditions.

Effects of pregnancy and lactation prebiotics supplementation on infant allergic disease: A randomized controlled trial

BackgroundIngestion of prebiotics during pregnancy and lactation may have immunomodulatory benefits for the developing fetal and infant immune system and provide a potential dietary strategy to reduce the risk of allergic diseases. ObjectiveThe aim of this trial was to determine whether maternal supplementation with dietary prebiotics reduces the risk of allergic outcomes in infants with hereditary risk. MethodsWe undertook a double-blind, randomized controlled trial in which pregnant women were allocated to consume prebiotics (14.2g daily of galacto-oligosaccharides and fructo-oligosaccharides in ratio 9:1) or placebo (8.7g daily maltodextrin) powder from <21 weeks gestation until 6-months postnatal during lactation. Eligible women had infants with a first-degree relative with a history of medically diagnosed allergic disease. The primary outcome was infant medically diagnosed eczema by 1-year of age, and secondary outcomes included allergen sensitization, food allergy, and recurrent wheeze by 1-year of age. Results652 women were randomized between June 2016 and November 2021 (n=329 prebiotics, n=323 placebo). There was no significant difference between groups in the percentage of infants with medically diagnosed eczema by 1-year of age (prebiotics 31.5% (103/327 infants) compared to placebo 32.6% (105/322 infants); adjusted relative risk 0.98 (95% CI 0.77, 1.23; p=0.84). Secondary outcomes and safety measures also did not significantly differ between groups. ConclusionWe found little evidence that maternal prebiotics supplementation during pregnancy and lactation reduces the risk of infant medically diagnosed eczema by 1-year of age in infants who are at hereditary risk of allergic disease.