Familial Cancer最新文献

{"title":"Development and pilot testing of AYA-RISE, a risk information and screening education intervention for adolescents and young adults with cancer risk syndromes.","authors":"Junne Kamihara, Lauren Fisher, Jaclyn Schienda, Rebecca Vanderwall, Moran Snir, Guy Snir, Emilie Simmons, Andrew Khalaj, Evan Goler, Kayla V Hamilton, Christopher C Porter, Bojana Pencheva, Joshua D Schiffman, Luke D Maese, Wendy Kohlmann, Tara O Henderson, Judy E Garber, Lisa R Diller, Ami V Desai, Sarah Savage, James L Klosky, Huma Q Rana, Jennifer W Mack","doi":"10.1007/s10689-025-00525-0","DOIUrl":"10.1007/s10689-025-00525-0","url":null,"abstract":"<p><p>Genetic testing is increasingly recommended for adolescents and young adults (AYAs) with cancer; however, no AYA-specific models for cancer risk communication have been developed. We developed a chatbot-based patient- and family-centered cancer risk communication tool, the AYA-RISE (AYA-Risk Information and Screening Education) intervention for AYAs aged 12–24 years.The intervention was developed together with AYAs with cancer risk syndromes, their family members, and clinicians, using Invitae’s Gia® chatbot (study Phase 1). 17 AYAs participated in a group discussion and completed surveys for input regarding development. Content was developed for 9 different syndromes. AYA-RISE was then refined after iterative input (Phase 2) and evaluated for feasibility and preliminary outcomes in a pilot study (Phase 3).100% of AYAs used the intervention through a point at which risk information was presented via the chatbot and portal demonstrating enrollment and chatbot use feasibility. Our threshold for acceptability was exceeded, with a post-test Acceptability of Intervention Measure (AIM) score of > 4 by 80% of AYAs. In the pre-visit survey, 40% of AYAs correctly reported risk of cancer by age 30, and 20% correctly reported lifetime cancer risk. Following the visit and use of the chat, 60% correctly reported risk of cancer by age 30 and 90% correctly reported lifetime risk. No significant differences in participant pre (3.4) and post (3.6, p=.34) distress thermometer mean scores were observed.The AYA-RISE intervention was feasible and acceptable for use by AYAs. Preliminary outcomes included improved knowledge when used in conjunction with a cancer risk clinic visit, without increasing distress. A randomized trial is currently ongoing.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"11"},"PeriodicalIF":2.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12830487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029009","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 renal cell carcinoma surveillance protocols: a review of the literature and proposed recommendations.","authors":"Miguel Miranda, Catarina Ferreira, Miguel Fernandes, Filipe Lopes, André Ye, Ana Berta Sousa, Luís Costa, José Palma Dos Reis, Tito Palmela Leitão","doi":"10.1007/s10689-025-00527-y","DOIUrl":"10.1007/s10689-025-00527-y","url":null,"abstract":"<p><p>Hereditary renal cell carcinoma (hRCC) syndromes represent a small but significant proportion of renal cancer cases, accounting for 5-8%. They are characterized by distinct genetic etiologies, early-onset presentations, and unique clinical features. Timely identification and surveillance of at-risk individuals are essential to improving outcomes, as early detection facilitates interventions at a localized stage. However, existing recommendations are highly variable and often lack robust evidence. This extensive review consolidates current knowledge on major hRCC syndromes, namely the von Hippel-Lindau (VHL) disease, hereditary papillary renal carcinoma (HPRC), fumarate hydratase deficient RCC (FHRCC), and Birt-Hogg-Dubé (BHD) syndrome, and their associated screening protocols. Through a comprehensive literature review, we summarize the cumulative risks, tumor growth patterns, and imaging recommendations for each syndrome, highlighting the challenges posed by their rarity and heterogeneous presentations. Based on these findings, we propose a standardized surveillance protocol tailored to each syndrome's risk profile, balancing early detection with the minimization of patient burden and healthcare costs. These recommendations emphasize the importance of multidisciplinary management in tertiary care centers to ensure optimal outcomes.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"10"},"PeriodicalIF":2.1,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948709","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":"Beyond 1100delC: distinct CHEK2 variants and unique cancer phenotypes in Northeast Brazil.","authors":"Mariana Macambira Noronha, Pedro Robson Costa Passos, Valbert Oliveira Costa Filho, Thais Baccili Cury Megid, Fernanda Teresa de Lima, Danielle Calheiros Campelo Maia","doi":"10.1007/s10689-025-00526-z","DOIUrl":"10.1007/s10689-025-00526-z","url":null,"abstract":"<p><p>The CHEK2 gene confers a moderate risk for breast cancer, but existing knowledge is largely based on the European founder variant, 1100delC. This study aimed to characterize the distinct phenotypes associated with unique CHEK2 variants in Brazilian families. In this cross-sectional study, 1055 patients meeting criteria for Hereditary Breast and Ovarian Cancer syndrome underwent germline multigene panel testing. Pathogenic/likely pathogenic variants (PVs) were found in 141 patients (13.4%), of whom 13 (9.2%) had a CHEK2 PVs. Subsequent family cascade testing brought the total number of individuals studied to 57. Three distinct CHEK2 PVs were identified: c.846 + 1G > C, c.349 A > G, and c.593-1G > T. While breast cancer was the most frequent tumor, specific PVs correlated with different cancer spectra. The c.349 A > G variant showed an enrichment for papillary thyroid cancer. In contrast, the c.846 + 1G > C variant was associated with melanoma, prostate, and testicular cancer, in addition to breast, colon, and kidney cancers. These findings suggest that different CHEK2 PVs may confer distinct cancer risks. Investigating these variants across diverse populations is crucial for refining phenotype characterization and improving genetic counseling as access to genetic testing expands.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"8"},"PeriodicalIF":2.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911168","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":"Japanese version of MICRA: introduction of the Shizuoka Cancer Center version.","authors":"Hiroyuki Matsubayashi, Rina Harada, Eiko Ishihara, Yoshimi Kiyozumi, Satomi Higashigawa, Reiko Suzuki, David Cella, Jason Bredle, Lillian Savic, Paul Cella","doi":"10.1007/s10689-025-00524-1","DOIUrl":"10.1007/s10689-025-00524-1","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"9"},"PeriodicalIF":2.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911165","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":"Description of six cases of melanoma in 512 patients with germline pathogenic variants in the TP53 gene.","authors":"Elisabeth de A C Callegaro, Janina Pontes Pisani, Vanessa Monteleone, Maria Isabel Achatz","doi":"10.1007/s10689-025-00517-0","DOIUrl":"10.1007/s10689-025-00517-0","url":null,"abstract":"<p><p>Li-Fraumeni Syndrome (LFS) is an autosomal dominant condition associated with germline pathogenic variants in the tumor suppressor gene TP53. Carriers have a higher risk of developing multiple primary tumors and a broad spectrum of cancers. The main tumors include premenopausal breast cancer, sarcomas, adrenocortical carcinoma and central nervous system tumors. Melanoma is a recognized but uncommon manifestation of LFS, with few reports in the literature linking the syndrome to this malignancy. The main objective of this study is to evaluate the occurrence of melanoma in patients carrying the germline pathogenic variant in the TP53 gene, registered in the Brazilian Li-Fraumeni Syndrome Study (BLISS) database from 2018 to 2023. From our database, six out of 512 patients developed melanoma, with melanoma representing the sole clinical manifestation of LFS in half of these patients. Of the 512 patients with LFS, 417 were carriers of the R337H variant, and among them, three patients developed melanoma. Three melanomas were detected during routine surveillance with total-body photography and digital dermoscopy. This study shows that melanoma is one of the manifestations of LFS, highlighting the importance of its screening within the Toronto protocol. It is essential for healthcare professionals who manage patients with LFS to recognize this risk in order to enable early diagnosis and identification of precursor lesions.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"7"},"PeriodicalIF":2.1,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818351","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":"Surgery in NF2-Schwannomatosis.","authors":"Michel Kalamarides, Omar Pathmanaban, Matthieu Peyre, Andrew Thomas King","doi":"10.1007/s10689-025-00522-3","DOIUrl":"10.1007/s10689-025-00522-3","url":null,"abstract":"<p><p>NF2-Schwannomatosis (NF2-SWN) is a disease characterized by multiple tumors of the central and peripheral nervous system. Surgery remains an important treatment option, sometimes performed on an urgent basis, but usually planned within the context of complex multi-tumour burden and morbidity. It is difficult to provide a comprehensive generic decision tree because each patient has a unique disease burden, but we will detail in this review the therapeutic indications for each tumor type, vestibular schwannomas, meningiomas, spinal schwannomas and meningiomas, spinal ependymomas and peripheral schwannomas. The experience of the multidisciplinary team impact outcomes in this rare disease and centralized care has been shown to improve the disease course.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"6"},"PeriodicalIF":2.1,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793718","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":"Functional characterization of splice variants in hereditary breast and ovarian cancer susceptibility genes.","authors":"Laura Rosado-Jiménez, Younes Mestre-Terkemani, Ángeles García-Aliaga, María D Sarabia-Meseguer, Miguel Marín-Vera, José A Macías-Cerrolaza, Pilar Sánchez-Henarejos, María R García-Hernández, Marta Zafra-Poves, Beatriz C Álvarez-Abril, Carmen B López-Sánchez, María P Moya-Martínez, Patricia Pascual-Gilabert, Ana M Cerón-Moreno, Verónica Castillo-Guardiola, David Antón-Martínez, Francisco Ayala-de la Peña, José L Alonso-Romero, José A Noguera-Velasco, Francisco Ruiz-Espejo","doi":"10.1007/s10689-025-00521-4","DOIUrl":"10.1007/s10689-025-00521-4","url":null,"abstract":"<p><p>Hereditary breast and ovarian cancer (HBOC) is an autosomal dominant cancer predisposition syndrome primarily associated with germline mutations in BRCA1 and BRCA2. Nevertheless, the implementation of multigene panels using Next Generation Sequencing (NGS) has expanded the mutational spectrum for this hereditary syndrome. As a result, the number of variants of uncertain clinical significance (VUS) has increased, and their functional and clinical interpretations remains a challenge for genetic counseling. This article reports three splice variants in susceptibility genes detected in women diagnosed with invasive ductal breast cancer. According to in silico predictions, these splicing-disrupting mutations in cancer susceptibility genes are likely to be pathogenic. Splicing functional assays were performed by reverse transcription polymerase chain reaction (RT-PCR) followed by capillary electrophoresis and Sanger sequencing. The characterization of these splicing events has enabled the identification of variants susceptible to alternative or abnormal splicing and their clinical classification according to the consensus criteria of the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP). This research increases our current knowledge about splice variants, thereby improving diagnostic performance and their clinical classification to support appropriate genetic counseling.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"5"},"PeriodicalIF":2.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774028","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":"\"It's not any one thing, it's always all of them, all at the same time\": quality of life in NF2-related schwannomatosis from patient and clinician perspectives.","authors":"Sophia C Carias, Frank D Buono, Liesel Von Imhof, Sneha M Yelamanchili, Hilary Chan, Kaleb H Yohay, P Leia Nghiemphu, Dusica Babovic-Vuksanovic, Scott R Plotkin, Vanessa L Merker","doi":"10.1007/s10689-025-00520-5","DOIUrl":"10.1007/s10689-025-00520-5","url":null,"abstract":"<p><p>While the physical manifestations of NF2-related schwannomatosis (NF2-SWN) have been well documented, there are a limited number of qualitative studies on health-related quality of life in NF2-SWN. The present study sought to explore the cumulative impact of symptoms, treatments, and healthcare on the quality of life of individuals with NF2-SWN. We interviewed 16 adolescent and adult patients with NF2-SWN enrolled in the INTUITT-NF2 clinical trial and 10 clinicians with NF2-SWN expertise from the United States, United Kingdom, and Australia. Analysis of patient and clinician interviews yielded five overall themes: (1) impacts on daily living, (2) impacts on life roles, (3) impacts on relationships and social integration, (4) impacts on psychological and emotional wellbeing, and (5) burden of treatment and healthcare. Multiple symptom areas contributed to impairments in quality of life across each theme. These findings reveal that quality of life in NF2-SWN is shaped not only by individual symptoms, but by their complex, cumulative impact-highlighting the urgent need for disease-specific tools and holistic care approaches that reflect the lived realities of patients across the lifespan.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"4"},"PeriodicalIF":2.1,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762761","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":"\"Choosing the main character\": healthcare professionals' attitudes towards counselling patients about risk disclosure to relatives in the era of mainstream cancer genetic testing.","authors":"Anna Öfverholm, Matilda Liljedahl, Agnes Elmberger, Per Karlsson, Anna Rosén","doi":"10.1007/s10689-025-00516-1","DOIUrl":"10.1007/s10689-025-00516-1","url":null,"abstract":"<p><p>PURPOSE: This study explored healthcare professionals’ attitudes toward counselling patients on disclosing genetic cancer risk to relatives. Genetic counselling practices in Sweden are undergoing significant changes due to the increased use of genetic testing to assess hereditary risk and the implementation of mainstreamed testing in oncology care. These developments require an assessment of healthcare professionals’ perceived roles and responsibilities when working with patients with hereditary risk. Best practices need to be developed to effectively support risk disclosure, and subsequently risk management, to relatives. METHOD: Data was collected through interviews with oncologists, gynaecologists, surgeons, clinical geneticists, and genetic counsellors, working in oncology care or at cancer genetics units. Data was analysed using reflective thematic analysis. RESULTS: The results are presented as four positions that healthcare professionals take, describing their attitudes towards counselling patients about risk disclosure to relatives. The position depends on whether they perceive healthcare or the patient as ultimately responsible for risk information reaching relatives, and whether their focus is on the patient or the at-risk relatives. There are several stakeholders involved, and hence 'characters in play'. CONCLUSION: These results could serve as a basis for discussions on roles and responsibilities, while developing best practices regarding genetic counselling on hereditary cancer risk communication.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"3"},"PeriodicalIF":2.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12700921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741825","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":"Pathogenic CDKN2A germline variants are rare in a cohort of unselected pancreatic cancer patients from Pakistan.","authors":"Shumaila Arif, Noor Muhammad, Humaira Naeemi, Muhammad Usman Rashid","doi":"10.1007/s10689-025-00515-2","DOIUrl":"10.1007/s10689-025-00515-2","url":null,"abstract":"<p><p>Pancreatic cancer is a highly aggressive malignancy, with 10%-20% of cases linked to inherited genetic risk factors. Pathogenic variants (PVs) in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene have been associated with pancreatic cancer among Caucasians. However, data from South Asians are lacking. We investigated the prevalence of CDKN2A germline variants in 200 consecutively and prospectively enrolled, unselected pancreatic cancer patients from Pakistan. Comprehensive variant detection was performed using high-resolution melting analyses followed by DNA sequencing. Novel variants were investigated for pathogenicity using in-silico tools, and potentially functional variants were screened in 200 healthy controls. Five unique CDKN2A variants were identified, including one novel synonymous variant c.285G > T (p.Val95Val), one missense variant c.442G > A (p.Ala148Thr), one intronic variant (c.150 + 32A > T), and two variants (c.*29G > C and c.*69C > T) in the 3' untranslated region. No PVs in CDKN2A were detected. All variants were classified as benign, except the novel synonymous variant (p.Val95Val), which was categorized as a variant of uncertain significance (VUS) based on in-silico protein function prediction scores (Revel 0.38; PhyloP 2.88). This variant was identified in a 61-year-old male patient of Punjabi ethnicity with Grade 2 periampullary ductal adenocarcinoma with lymphovascular invasion and was absent in 200 healthy controls. Our study showed that CDKN2A PVs are very rare among unselected Pakistani pancreatic cancer patients, suggesting a negligible contribution to inherited pancreatic cancer risk in this population.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 1","pages":"2"},"PeriodicalIF":2.1,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687176","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}