Familial Cancer最新文献

{"title":"Factors influencing public willingness to participate in population-based hereditary cancer genetic testing: a qualitative study of public preferences.","authors":"Diego R Sanchez-Vazquez, Jonathan Avery, Whitney Qualls, Colene Bentley, Helen McTaggart-Cowan, Julianne McLeod, Lesa Dawson, Stuart Peacock","doi":"10.1007/s10689-026-00555-2","DOIUrl":"10.1007/s10689-026-00555-2","url":null,"abstract":"<p><p>Over 97% of individuals with hereditary cancer predisposition remain unidentified, limiting access to life-saving prevention and screening. In British Columbia (BC), access to publicly funded genetic testing is restricted to individuals with a family history of cancer. A novel solution, population-based testing (PBT), would remove the family history requirement, providing unrestricted access for all residents. This qualitative study explored the factors influencing public willingness to participate in a PBT program in BC. We recruited BC residents through a market research company to participate in online, one-to-one, semi-structured interviews. Interested individuals were purposively sampled to ensure maximum representation in terms of age, ethnicity, and residence. Transcribed sessions were analyzed in NVivo v14. A thematic analysis was employed within a descriptive qualitative approach to identify and interpret patterns within the transcripts. Twenty 60-min interviews were conducted on Zoom from June to December 2024. Three key factors influenced potential participation in PBT: perceived utility of genetic testing, ethical and privacy concerns, and health system support. The perceived utility of genetic testing influenced individuals to assess genetic risk to reduce uncertainty and manage their health. Ethical concerns, such as the misuse of genetic data by insurers or employers, complicate decision-making. Health system support included affordable testing, continuity of care, and emotional and educational resources. Novel PBT programs should address cultural, socioeconomic and geographical inequities, while safeguarding the privacy of the public. Key to success will be the availability of emotional, educational, and financial support for individuals using PBT.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new c.681dup RUNX1 variant in familial leukemia.","authors":"Maria Crocioni, Carlotta Nardelli, Anair Graciela Lema Fernandez, Valentina Bardelli, Valentina Pierini, Caterina Matteucci, Eloise Beggiato, Matteo Olivi, Valentina Vigliani, Alessandra Pelle, Giuseppe Lanzarone, Cristina Mecucci","doi":"10.1007/s10689-026-00550-7","DOIUrl":"10.1007/s10689-026-00550-7","url":null,"abstract":"<p><p>Constitutional RUNX1 gene variants are associated with Familial Platelet Disorder (FPD) and predispose to a variety of hematological malignancies, included Acute Myeloid Leukemia (AML) and, albeit less frequently, Acute Lymphoblastic Leukemia (ALL). In this study, we report on a proband with primary diagnosis of AML, followed by T-ALL after transplant, and a positive familial history for leukemia over three generations. A new heterozygous germline pathogenic RUNX1 (c.681dup, p.(Leu228ThrfsTer33)) variant was found in the proband and his affected mother.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hereditary gynecological cancer management in women with Lynch syndrome: a survey across Europe.","authors":"Kevin J J Kwinten, Joanne A de Hullu, Nicoline Hoogerbrugge, Anne M van Altena","doi":"10.1007/s10689-026-00546-3","DOIUrl":"10.1007/s10689-026-00546-3","url":null,"abstract":"<p><p>We aim to compare clinical practices in the gynecological management of women with Lynch syndrome across Europe and assess the need for multidisciplinary gynecological care for this high-risk population. European gynecologists involved in the clinical care of women with Lynch syndrome were invited to complete a cross-sectional survey regarding their clinical practices and organization of care. All participating gynecologists were based in hospitals that are members of the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS). A total of 33 gynecologists (57%) from 25 unique hospitals across 12 countries participated in the survey. National guidelines on the gynecological management of women with Lynch syndrome were absent in a significant number of European countries. Local multidisciplinary team meetings were available in 61% of hospitals. Considerable heterogeneity was reported in the organization of care, as well as in surveillance, prevention, and treatment strategies. Standardized European guidelines for the gynecological care of women with Lynch syndrome are warranted to promote uniformity. Gynecologists specialized in hereditary cancer should take the lead in developing and implementing these guidelines. Hospitals managing women with Lynch syndrome should have the resources to organize multidisciplinary team meetings, which are crucial for the effective implementation of these guidelines and the improvement of personalized care.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-evaluating hereditary breast and ovarian cancer risk: clinical impact of updated multigene panel sequencing and genetic counseling.","authors":"Julie Isabelle Plougmann Gislinge, Anna Byrjalsen, Klara Vinsand Naver, Helle Vibeke Clausen, Pernille Ravn, Kresten Rubeck Petersen, Karin A W Wadt","doi":"10.1007/s10689-026-00547-2","DOIUrl":"10.1007/s10689-026-00547-2","url":null,"abstract":"<p><p>An increased lifetime risk of ovarian cancer is observed among women with a family history of ovarian cancer, with or without breast cancer, as well as among carriers of pathogenic germline variants in ovarian cancer (OC) predisposition genes. Over the past two decades, additional OC–associated genes beyond BRCA1/2 have been identified, highlighting the need for updated genetic evaluation in women previously classified as high-risk without a known PV to ensure correct diagnosis and prevent overtreatment. This retrospective, quality assurance cohort study aimed to evaluate whether updated multigene panel sequencing and genetic counseling improve risk stratification. All women enrolled in the OC surveillance program at Copenhagen University Hospital Herlev between 2018 and 2023 and received counseling prior to the implementation of the revised 2017 guidelines in Denmark, were included. Among 674 women (median age 40.9), 174 had a BRCA1 PV, 168 had a BRCA2 PV, 55 had PVs in moderate-risk genes, and 277 were enrolled based on family history of OC ± BC alone. Of these 277, 216 (78%) underwent updated genetic testing and counselling; 165 (76%) had no increased risk of OC and were released from gynecological surveillance. Over a mean follow-up of 48 months, none developed OC, and one developed BC, corresponding to a negative predictive value of 99% for the updated risk assessment. Updated genetic testing and counseling significantly improve risk stratification in women previously classified as increased risk of OC based solely on family history. This supports re-evaluation of at-risk women and families to guide appropriate surveillance, reduce unnecessary follow-up and interventions, and align clinical practice with evolving guidelines.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cascade testing as the missing link in cancer prevention among Lynch syndrome families.","authors":"Lea Godino, Giulia Erini, Giovanni Innella, Sara Miccoli, Simona Ferrari, Pamela Magini, Luca Caramanna, Martina Preite, Veronica Simoni, Daniela Turchetti","doi":"10.1007/s10689-026-00549-0","DOIUrl":"10.1007/s10689-026-00549-0","url":null,"abstract":"<p><p>This study examined the uptake and timing of cascade testing in families with Lynch syndrome followed at a single Genetics Service in Northern Italy, with the aim of identifying family and individual factors that may influence uptake of testing in at-risk relatives. All living blood relatives aged ≥ 18 years and eligible for the first step of cascade testing were included. Forty-eight families were examined. Most probands were women (77.1%) mainly affected by endometrial (55.3%) or colorectal cancer (42.6%); the branch segregating the pathogenic variant was known/suspected in 51.1% of families. Overall, the cascade testing uptake was 19.5%. At the family level, uptake ranged from 0 in 47.9 to 100% in 4.2% of families. Binary logistic regression confirmed age and degree of kinship as significant predictors; younger relatives were more likely to undergo testing (OR = 0.97 per year, p < .001), while testing likelihood declined across kinship degrees (12-month testing: 27.7% first-degree, 10.4% second-degree, 5.7% more distant relatives; Log Rank p < .001) with Odds Ratios of 0.27 for second-degree and 0.07 for third-degree or beyond. Neither sex (p = .487) nor health status (p = .271) were significantly associated with uptake. Kaplan–Meier analysis showed that uptake occurred mostly within the first 12 months after the proband’s result (86.7% of those tested), after which it plateaued. These real-world findings highlight substantial gaps in cascade testing implementation and provide evidence to guide future strategies aimed at increasing uptake and strengthening family communication of genetic risk in the Italian context.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention strategies for hereditary gynaecological cancer in Lynch syndrome.","authors":"Kevin J J Kwinten, Jean-Ellen Johnson, Anne M van Altena, Nicoline Hoogerbrugge, Emma J Davidson, Joanne A de Hullu","doi":"10.1007/s10689-026-00548-1","DOIUrl":"10.1007/s10689-026-00548-1","url":null,"abstract":"<p><p>Lynch syndrome is a hereditary cancer predisposition condition associated with an elevated lifetime risk of colorectal, endometrial, ovarian, and several other malignancies. This review provides an updated overview of evidence-based prevention strategies for gynaecological cancers in patients with Lynch syndrome. Risk-reducing hysterectomy with bilateral salpingo-oophorectomy is the most effective intervention for lowering cancer incidence and mortality, but is associated with surgical morbidity and requires careful consideration of reproductive plans and the adverse consequences of premature menopause. Gynaecological surveillance using transvaginal ultrasound and endometrial biopsy is widely implemented as an alternative; however, available evidence is heterogeneous and indicates no benefit in reducing mortality. Novel approaches—such as biomarker-based detection using DNA methylation analysis of cervicovaginal samples, liquid biopsy techniques, and microbiome profiling—offer promising, non-invasive alternatives but require prospective validation in Lynch-specific populations. Chemoprevention with hormonal agents and aspirin may reduce cancer risk, while vaccine-based prevention strategies are under active investigation. Adoption of a healthy lifestyle is recommended for overall health, although its impact on gynaecological cancer risk in Lynch syndrome remains uncertain. Future research should prioritise prospective trials to establish optimal cancer prevention protocols, validate novel biomarkers and preventive cancer vaccine strategies, and evaluate the long-term effectiveness, acceptability, and cost-effectiveness of combined preventive approaches to improve outcomes in this high hereditary-risk population.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic prediction model for detecting advanced rectal polyps after ileorectal anastomosis in familial adenomatous polyposis: a dual-center retrospective study.","authors":"Zhilin Liu, Xingjie Gao, Shuling Chen, Linfu Zheng, Binbin Xu, Gaozhen Deng, Wen Wang, Kun Lin, Chushu Li, Zhou Ye, Dazhou Li","doi":"10.1007/s10689-026-00545-4","DOIUrl":"10.1007/s10689-026-00545-4","url":null,"abstract":"<p><p>Familial adenomatous polyposis (FAP) patients who undergo ileorectal anastomosis (IRA) remain at risk for advanced rectal neoplasia. Early identification of polyps < 10 mm is crucial to prevent metachronous rectal cancer. This study aimed to develop an endoscopic prediction model using mucosal phenotypic features to identify advanced diminutive rectal polyps in FAP patients post-IRA. This dual-center retrospective study included 48 FAP patients who underwent IRA and endoscopic surveillance from 2018 to 2024. A total of 452 rectal polyps < 10 mm were evaluated using high-definition white-light endoscopy, NBI, dye-based chromoendoscopy, and magnifying endoscopy. Data from Center 1 were split into a training set (80%) and validation set (20%), while Center 2 served as an external validation cohort. Significant variables (P < 0.05) from univariate analysis were entered into multivariable logistic regression. In the overall cohort and the APC pathogenic mutation subgroup, nomograms were developed and evaluated using ROC curves, calibration curves, and decision curve analysis (DCA). Independent predictors of advanced polyps included chicken-skin mucosa (OR = 2.50, P < 0.01), JNET type 2 A-2B low (OR = 3.39, P <  0.01), erosion/ulceration (OR = 1.68, P = 0.02), and pit pattern III-L/IV (OR = 2.47, P < 0.01). The nomogram showed good discriminative ability with AUCs of 0.822 (training), 0.806 (internal validation), and 0.815 (external validation). Separate prediction models were developed for all IRA-postoperative FAP patients and the APC pathogenic mutation subgroup, integrating four endoscopic features to accurately identify advanced diminutive rectal polyps, thereby reducing the risk of malignancy in patients.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic testing for hereditary breast and ovarian cancer in the Murcian population using a comprehensive NGS panel.","authors":"Y Mestre Terkemani, L Rosado Jiménez, A García Aliaga, M D Sarabia Meseguer, M Marín Vera, J A Macías Cerrolaza, P Sánchez Henarejos, M R García Hernández, M Zafra Poves, B Alvarez Abril, E García Torralba, C B López Sánchez, M P Moya Martínez, M A Moreno Locubiche, D A Sánchez Martínez, T A Quirós Figelló, A M Cerón Moreno, M Expósito García, D Antón Martínez, E Martínez Barba, F Ayala de la Peña, J L Alonso Romero, J A Noguera Velasco, F Ruiz Espejo","doi":"10.1007/s10689-026-00544-5","DOIUrl":"10.1007/s10689-026-00544-5","url":null,"abstract":"<p><p>Traditionally, hereditary breast and ovarian cancer syndrome (HBOC) has been associated with germline pathogenic or likely pathogenic variants (PV/LPV) in BRCA1 and BRCA2. However, growing evidence indicates that this condition is genetically heterogeneous, and that PV/LPV in additional cancer predisposition genes also contribute significantly to disease susceptibility. In this study, 414 HBOC index cases (ICs) from the Region of Murcia, who fulfilled the 2019 Spanish Society of Medical Oncology (SEOM) criteria, were analyzed using next-generation sequencing (NGS). A 50-gene panel was applied, containing a total of 20 clinically actionable genes recommended by the National Comprehensive Cancer Network (NCCN) for HBOC. The study achieved a diagnostic yield of 15% based solely on the 20 clinically actionable genes included in the panel, with the highest detection rate observed among patients with co-occurring breast and high-grade serous epithelial ovarian cancer. Notably, applying only criteria involving a personal history of breast cancer from the 2019 SEOM guidelines limited the identification of HBOC patients carrying PV/LPV. It was also observed that BRCA genes contributed more to HBOC than non-BRCA genes (60% and 40%, respectively). Finally, re-evaluation of variants of uncertain significance (VUS) led to a substantial reduction in their number, with 25.38% of the initially identified VUS reclassified as benign or likely benign and 6 of the 97 remaining variants (6.2%) prioritized after applying a prioritization algorithm. This study confirms the importance of limiting HBOC genetic testing to clinically actionable genes in routine clinical practice. The re-evaluation and the prioritization of VUS are also essential, since they allow clinical laboratories to manage their resources more efficiently.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uptake and timing of risk-reducing gynecologic surgery among individuals with Lynch syndrome identified via population screening.","authors":"Jazmine L Gabriel, Michelle Pistner Nixon, Olivia Steinmetz, Gina Rossi, Abigail Glynn, Lavanya Garnepudi, Annum Hayat, Beatriz Abello, Kaitlin Toal, Katrina M Romagnoli","doi":"10.1007/s10689-026-00543-6","DOIUrl":"10.1007/s10689-026-00543-6","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors affecting compliance with pancreas surveillance in patients with familial/genetic risk.","authors":"Emy Abou Sleiman, Hassan Sinan, Eun Ji Shin, Marcia Irene Canto, Michael Goggins","doi":"10.1007/s10689-026-00542-7","DOIUrl":"10.1007/s10689-026-00542-7","url":null,"abstract":"<p><strong>Background: </strong>To achieve early pancreatic cancer detection, patients with familial/genetic predisposition need to maintain regular surveillance with EUS and/or MRI for many years. Factors influencing compliance with pancreatic surveillance compliance are not well understood.</p><p><strong>Methods: </strong>We conducted a one-time cross-sectional survey of patients enrolled in the ongoing Cancer of the Pancreas Screening 5 (CAPS5) study at Johns Hopkins Hospital. Patients answered a 21-item questionnaire that assessed demographic, financial, psychological, and clinical factors that could potentially affect their compliance with pancreatic surveillance. Descriptive, univariate, and multivariate analysis were performed to determine factors independently associated with compliance with surveillance recommendations.</p><p><strong>Results: </strong>The survey was sent to 996 HRI in April 2025; 774 responded (mean respondent age 65.25 ± 10.22 years, 62.3% female); 88.7% reported being compliant. In multivariate analysis, compliance was significantly lower among participants reporting personal, work-related, or logistical challenges with making/keeping appointments (p < 0.01), having significant insurance copayments (p = 0.017), or reporting fear of a pancreatic cancer diagnosis (p = 0.013). Reporting that pancreatic surveillance tests provided reassurance (p = 0.001), or provoked anxiety (p = 0.021) were also associated with higher compliance, as was having a strong support system (p = 0.03). Patients who preferred EUS over MRI were also significantly more likely to report being compliant (p = 0.011). Finally, patients who had undergone cancer susceptibility gene testing were more compliant than those who had not (p = 0.016), though there was no significant difference in compliance rates among gene-test-positive versus gene-test-negative patients (p = 0.82).</p><p><strong>Conclusion: </strong>Recognizing and addressing factors associated with reduced compliance may help improve compliance with pancreatic surveillance.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}