Familial Cancer[JOURNAL]
Sun
200 papers
Endoscopic prediction model for detecting advanced rectal polyps after ileorectal anastomosis in familial adenomatous polyposis: a dual-center retrospective study.
Liu Z, Gao X, Chen S … +8 more , Zheng L, Xu B, Deng G, Wang W, Lin K, Li C, Ye Z, Li D
Fam Cancer · 2026 Mar · PMID 41874735 · Publisher ↗
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...
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.
Genetic testing for hereditary breast and ovarian cancer in the Murcian population using a comprehensive NGS panel.
Mestre Terkemani Y, Rosado Jiménez L, García Aliaga A … +21 more , Sarabia Meseguer MD, Marín Vera M, Macías Cerrolaza JA, Sánchez Henarejos P, García Hernández MR, Zafra Poves M, Alvarez Abril B, García Torralba E, López Sánchez CB, Moya Martínez MP, Moreno Locubiche MA, Sánchez Martínez DA, Quirós Figelló TA, Cerón Moreno AM, Expósito García M, Antón Martínez D, Martínez Barba E, Ayala de la Peña F, Alonso Romero JL, Noguera Velasco JA, Ruiz Espejo F
Fam Cancer · 2026 Mar · PMID 41870673 · Publisher ↗
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 co...
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.
Uptake and timing of risk-reducing gynecologic surgery among individuals with Lynch syndrome identified via population screening.
Gabriel JL, Nixon MP, Steinmetz O … +7 more , Rossi G, Glynn A, Garnepudi L, Hayat A, Abello B, Toal K, Romagnoli KM
Fam Cancer · 2026 Mar · PMID 41863558 · Publisher ↗
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Factors affecting compliance with pancreas surveillance in patients with familial/genetic risk.
Abou Sleiman E, Sinan H, Shin EJ … +2 more , Canto MI, Goggins M
Fam Cancer · 2026 Mar · PMID 41848926 · Full text
BACKGROUND: 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 pancre...
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Recognizing and addressing factors associated with reduced compliance may help improve compliance with pancreatic surveillance.
Patient-derived outcome assessment of knowledge, communication, and management in those diagnosed with BAP1-tumor predisposition syndrome.
Godwin K, McElroy J, Senter L … +2 more , Byrne L, Abdel-Rahman MH
Fam Cancer · 2026 Mar · PMID 41843333 · Full text
Germline pathogenic variants in BAP1 are associated with BAP1 tumor predisposition syndrome (BAP1-TPDS), and an increased risk for different cancers and preneoplastic lesions. This study assessed the degrees of patient k...
Germline pathogenic variants in BAP1 are associated with BAP1 tumor predisposition syndrome (BAP1-TPDS), and an increased risk for different cancers and preneoplastic lesions. This study assessed the degrees of patient knowledge of BAP1-TPDS, patient-reported sharing of their genetic test results and diagnosis, and the degree of compliance with current management guidelines. A survey was sent to individuals with a germline pathogenic/likely pathogenic variant in BAP1 who are enrolled in a research registry at The Ohio State University. Knowledge about BAP1-TPDS was assessed utilizing a modified scale (KnowGene). Participants were asked about communication surrounding BAP1-TPDS with family members, and their current cancer surveillance. Forty-two (55%) subjects completed the survey with 25 (60%) having strong 80% knowledge of the syndrome, and 33 (79%) having at least 60% knowledge. All participants reported sharing their genetic result or diagnosis with at least one family member, primarily their first-degree relatives. Most of the cohort had undergone some recommended surveillance for BAP1-TPDS. In conclusion, BAP1-TPDS subjects are knowledgeable about the syndrome phenotype, highly communicative about their diagnosis with family members, and follow some recommended surveillance. Capturing patient-reported outcomes of BAP1-TPDS subjects is crucial for understanding their need for further education, resources, or support.
The gut microbiome as a biomarker and modifiable risk factor in Lynch Syndrome.
Colaco VS, Boleij A
Fam Cancer · 2026 Mar · PMID 41784899 · Full text
Lynch Syndrome (LS) is the most prevalent hereditary colorectal cancer syndrome, driven by germline mutations in DNA mismatch repair genes. Despite intensive colonoscopy surveillance, cancer risk among LS carriers remain...
Lynch Syndrome (LS) is the most prevalent hereditary colorectal cancer syndrome, driven by germline mutations in DNA mismatch repair genes. Despite intensive colonoscopy surveillance, cancer risk among LS carriers remains highly variable, suggesting additional modifiers beyond genetics. Emerging evidence implicates the gut microbiome as a potential biomarker and modifiable risk factor in LS-associated carcinogenesis. This review synthesizes current findings on taxonomic and functional microbiome alterations in LS carriers, highlighting early dysbiosis characterized by depletion of butyrate-producing taxa and enrichment of virulent species such as pks+ Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. These oncogenic microbes promote DNA damage, inflammation and epithelial hyperproliferation in the mismatch repair deficient context, accelerating tumorigenesis. Functional signatures such as colibactin genotoxicity appear more predictive than taxonomic diversity. However, methodological heterogeneity, small cohorts and lack of longitudinal data limit biomarker validation. Finally, we outline future research that should integrate multi-omics, spatial profiling and genotype-stratified designs to identify clinically actionable microbial signatures. Understanding microbiome and host interactions in LS could assist in improved risk stratification beyond current standard surveillance guidelines.
InSiGHT 2026 meeting: abstracts.
Fam Cancer · 2026 Mar · PMID 41770398 · Publisher ↗
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Improving care for Lynch syndrome patients: integrating surveillance into England's national bowel cancer screening programme.
Monahan KJ, Poo SX, Lalloo F
Fam Cancer · 2026 Feb · PMID 41746524 · Full text
Quality assurance, timeliness and equity of access to colonoscopy for people with Lynch syndrome (LS) in England has historically been highly variable. The LS-Bowel Cancer Screening Programme (LS-BCSP) launched in July 2...
Quality assurance, timeliness and equity of access to colonoscopy for people with Lynch syndrome (LS) in England has historically been highly variable. The LS-Bowel Cancer Screening Programme (LS-BCSP) launched in July 2023, delivers high quality colonoscopy to the average-risk population, from colonoscopists who have undergone high-level accreditation, utilising the existing average-risk BCSP infrastructure. Eligible individuals have a genetic diagnosis of LS. Comprehensive retrospective diagnoses of LS in England (since the 1990s) were ascertained from 17 regional genetics services. The National Disease Registration Service (NDRS) developed a registry of eligible individuals, and a portal for prospectively diagnosed cases. An existing national screening IT framework was adapted to incorporate disease-specific clinical pathway information, linked to existing national guidelines. Nationally standardised training for BCSP teams was delivered to > 2000 staff from 64 national screening centres in 2023. By November 2024, 10,913 eligible individuals were identified, with 150–250 new diagnoses added each month. A historical backlog of > 1000 patients overdue colonoscopy surveillance was cleared by January 2024. Diagnostic outcomes of LS patients from the first two years of LS-BCSP will be available to facilitate evaluation of the successes and failures of the LS_BCSP. This evaluation will include diagnostic outcomes, stratified by demographic and socioeconomic status, genotype, measures of colonoscopy quality and regional variation. This novel programme includes complete ascertainment of the national LS population in England, without requirement for referral. Individuals with LS now have access to high-quality, timely colonoscopy through an accredited programme which is quality-assured along the entire pathway.
From theory to practice: improving Lynch syndrome recognition through evidence-based education.
Sanduleanu-Dascalescu S, Dimofte G, Chiu HM … +3 more , Cotruta B, Morarasu S, Vasen H
Fam Cancer · 2026 Feb · PMID 41733729 · Publisher ↗
Although genomic medicine has improved understanding of Lynch Syndrome (LS), many challenges remain in translating the knowledge in clinical practice. Between 1 in 279 and 400 persons in general population carry a pathog...
Although genomic medicine has improved understanding of Lynch Syndrome (LS), many challenges remain in translating the knowledge in clinical practice. Between 1 in 279 and 400 persons in general population carry a pathogenic mutation in mismatch repair (MMR) genes linked to LS, but the vast majority remain undiagnosed. The clinical implementation gap arises from an interplay between physician factors, patient factors and logistic factors. In the first place, there is limited awareness and limited compliance among practicing physicians who often don’t recognize LS and don’t follow surveillance recommendations, missing opportunities to prevent cancer in affected persons and family members. One of the central problems lies in the current educational approach, particularly the lack of a curriculum on hereditary cancer syndromes during GI fellowship. Theoretical guidance alone is not actionable—it needs to be backed up by case-based practice with adequate provision both in terms of quantity and of insights. An evidence-based curriculum for achieving mastery standards on LS recognition and management shows early promise in fostering clinical transformation. Using repeat cycles of self-study and case-based practice with real-time feedback, learners can acquire base knowledge and problem-solving clinical decision skills faster and more effectively. This approach leads to a shift in practice. In the context of population screening programs for colorectal cancer (CRC) and gynecological cancers, this strategy can enhance the effectiveness of screening by reducing cancer incidence and mortality. Herein, we propose steps for the integration of LS screening into routine clinical practice, with particular focus on education.
Splenic hamartoma in two related patients with BAP1 tumour predisposition syndrome caused by a novel germline BAP1 p.(Gly128Arg) missense variant.
Ragnarsson KA, Garcia G, Jonasson JG … +5 more , Arnadottir GA, Reykdal SE, Arngrimsson R, Haraldsdottir S, Jonsson JJ
Fam Cancer · 2026 Feb · PMID 41712014 · Full text
BAP1 tumour predisposition syndrome (BAP1-TPDS) is a hereditary cancer syndrome caused by heterozygous pathogenic germline variants in BAP1. BAP1-TPDS is associated with an increased risk for various malignant tumours, t...
BAP1 tumour predisposition syndrome (BAP1-TPDS) is a hereditary cancer syndrome caused by heterozygous pathogenic germline variants in BAP1. BAP1-TPDS is associated with an increased risk for various malignant tumours, the core of which is uveal and cutaneous melanoma, malignant mesothelioma, and renal cell carcinoma. In BAP1-TPDS, the majority of disease-causing BAP1 variants are null variants, although missense variants have been reported. We report a patient with BAP1-TPDS caused by the novel germline BAP1 missense variant NM_004656.4:c.382G > A, p.(Gly128Arg). The patient developed BAP1-inactivated melanocytic tumours, clear-cell renal cell carcinoma, and splenic hamartoma. An incidental splenic hamartoma was detected in existing tissue slides from the patient's deceased first-degree relative, who was an obligate carrier for BAP1-TPDS. In both splenic hamartomas, loss of BAP1 nuclear staining was detected in a subset of cells on immunohistochemistry. To our knowledge, this is the first report with immunohistochemical data supporting biallelic loss of BAP1 as a contributing step in the development of a splenic hamartoma in a patient with BAP1-TPDS. It supports expanding the tumour spectrum of BAP1-TPDS to splenic hamartoma and possibly other benign splenic tumours.
Misinterpreting the results: patient misconceptions about genetic cancer risk after obstetrical carrier screening.
Raghunandan A, Iyer S, Dioun S … +6 more , Scholl J, Kalish RB, Primiano M, Ozarowski AL, Sharaf RN, Frey MK
Fam Cancer · 2026 Feb · PMID 41706374 · Publisher ↗
Obstetric carrier screening (OCS) is recommended for all individuals during pregnancy by leading professional societies. However, patient understanding of the scope and limitations of OCS remains poorly characterized, es...
Obstetric carrier screening (OCS) is recommended for all individuals during pregnancy by leading professional societies. However, patient understanding of the scope and limitations of OCS remains poorly characterized, especially with regards to inclusion of cancer-related genes on OCS panels. This quality improvement initiative evaluated pregnant patients' knowledge of their OCS results. We contacted 100 pregnant patients who had recently completed OCS and participated in a structured telephone interview following physician disclosure of results. When asked about the content of OCS, 52% of patients were unsure or incorrectly believed that cancer-related genes were included on the panel. After clarification of the specific genes and syndromes tested, 73% of patients reported that they would have elected to undergo hereditary cancer screening had it been offered concurrently with OCS. These findings reveal substantial gaps in patient comprehension of OCS and suggest that many pregnant patients incorrectly assume that cancer susceptibility genes are included in their testing. The high level of interest in hereditary cancer screening following clarification underscores pregnancy as a unique window of opportunity to expand access to cancer genetics. Integrating cancer risk assessment into obstetric care may improve uptake of preventive strategies and broaden the impact of genomics on women's health.
Does bilateral mastectomy affect clinical outcomes in BRCA1/2 mutation carriers with primary breast cancer? A systematic review and meta-analysis.
de Souza Wagner PH, Freitas Uchôa Matheus GT, Zimermann Kamitani H … +2 more , Azevedo de Carvalho PL, de Moraes FCA
Fam Cancer · 2026 Feb · PMID 41697510 · Publisher ↗
BACKGROUND: BRCA1/2-carriers—who account for 5–10% of breast cancer (BC) cases—face markedly elevated lifetime risks of BC. Among those diagnosed with primary breast cancer (PBC), these carriers confront a cumulative con...
BACKGROUND: BRCA1/2-carriers—who account for 5–10% of breast cancer (BC) cases—face markedly elevated lifetime risks of BC. Among those diagnosed with primary breast cancer (PBC), these carriers confront a cumulative contralateral breast cancer (CBC) risk of 40% within 10 years—alongside poorer overall survival (OS) and breast cancer–specific survival (BCSS). Whether contralateral risk-reducing mastectomy (CRRM) can improve OS, BCSS, and reduce CBC risk in this high-risk group remains unresolved. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis of cohort studies (PROSPERO:CRD420251024265). PubMed, Embase, Cochrane Library were searched through June 2025. Studies enrolled BRCA1/2-carriers with PBC, compared CRRM versus Non-CRRM, and reported OS, BCSS, or CBC risk. We pooled hazard ratio (HR) and risk ratio (RR) for these outcomes. Heterogeneity was quantified by I2. RESULTS: This meta‐analysis included nine cohort studies, encompassing BRCA1/2-carriers with PBC. In the OS analysis, including 3138 patients in the CRRM group versus 2,592 in the Non-CRRM group, CRRM presented a substantial survival benefit (HR 0.638; P < 0.001). BCSS (567 CRRM and 623 Non-CRRM patients), likewise demonstrated an advantage for the CRRM group (HR 0.601; P = 0.005). CBC risk, evaluated in 637 CRRM and 976 Non-CRRM patients, was reduced by 91% (RR 0.090; P < 0.001), reflecting an absolute risk reduction of 188 CBC events per 1000. CONCLUSION: CRRM confers substantial oncologic benefits, improving OS and BCSS and reducing CBC risk in BRCA1/2 carriers with PBC, and should be considered for this high-risk population, informing guideline recommendations.
Mental- and physical health, and general well-being in patients with polyposis syndromes: a scoping review.
Walton Bernstedt S, Jervaeus A, Höiom V … +1 more , Fritzell K
Fam Cancer · 2026 Feb · PMID 41689588 · Full text
Polyposis syndromes are associated with an increased lifelong cancer risk in several organs as well as a commitment to regular examinations and risk-reducing surgery of healthy organs, which can be compared to living wit...
Polyposis syndromes are associated with an increased lifelong cancer risk in several organs as well as a commitment to regular examinations and risk-reducing surgery of healthy organs, which can be compared to living with a constant health threat. More recently conducted research on the topic is scarce, and, therefore, this scoping review synthesized data of existing research on mental and physical health and general well-being from the patients’ perspectives. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was used. The search was conducted between January 2000 and October 2024, leading to the identification of 4138 studies. Of those, 39 studies met the inclusion criteria (1%), and of the 2214 included participants, 2108 had familial adenomatous polyposis. In order to analyze and synthesize relevant data, aspects of directed content analysis were applied. The findings show that patients exhibited mental and physical health in parity to population norms. However, feelings of vulnerability, anxiety, worry and fear, especially in younger participants were reported. In addition, decreased bowel and sexual function, food restrictions, body dissatisfaction, and physical attractiveness were evident. Regarding well-being, an altered lifestyle, work and social discrimination, insurance matters, concerns for family members and fertility were reported. Being female seemed to be related to mental health issues or vulnerability thereof. Appropriate screening tools, such as patient reported outcome measures (PROM), should be developed and implemented in a structured way to capture patients needs in clinical settings. Future research is needed for the rarer syndromes, represented to a limited extent in this review.
Single institution assessment of physician compliance and patient uptake with guideline directed aspirin therapy in the prevention of colorectal cancer in lynch syndrome.
Yudiski A, Rocha H, Liu E … +10 more , Dzeda M, Granja O, Haynes N, Woolley H, Conklin S, Shermanski G, Leicht A, Morland T, Wu K, Confer B
Fam Cancer · 2026 Feb · PMID 41661407 · Publisher ↗
Patients with Lynch syndrome (LS) have been shown to have up to an 60% lifetime risk of developing colorectal cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommend LS patients consider taking aspi...
Patients with Lynch syndrome (LS) have been shown to have up to an 60% lifetime risk of developing colorectal cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommend LS patients consider taking aspirin (ASA) daily to reduce their risk of colorectal cancer, which is primarily based on the Cancer Prevention Project 2 (CAPP-2) study results. In this study, we evaluated the uptake of guideline directed aspirin therapy among LS patients at Geisinger Inherited Risk Gastrointestinal clinic (IRGI). Medical records of 177 patients were retrospectively reviewed from May 2016 to December 2022. After excluding those with missing data or lost to follow-up, our study cohort consisted of 167 patients. Demographics, affected genes, clinical history, and ASA use were collected. Chi-square test and unpaired T-test were used to evaluate the association between various parameters and ASA use. With a median annual follow up of 36 months and adjustment for patients with relative and absolute contraindications to ASA, 58.5% (83/142) of patients were compliant with ASA therapy. Nearly half 49.4% (41/83) of ASA users took 81 mg daily, 1.2% (1/83) took 250 mg daily, 42.2% (35/83) took 325 mg daily and only 7.2% (6/83) reported taking > 600 mg daily. Relatively older patients were significantly more likely to take ASA compared to those not taking ASA (p-value = 0.025). The success of guideline focused discussion in encouragement of daily ASA use as primary prophylaxis in colorectal cancer amongst LS patients is likely multifactorial and beyond absolute medical contraindications.
Attenuated Li-Fraumeni syndrome with TP53 p.R181H in a Japanese patient with metastatic rectal adenocarcinoma: a case report.
Kasahara Y, Takahashi M, Kawamura Y … +17 more , Aoki Y, Niihori T, Kawamura M, Yamamoto S, Shirota H, Saijo K, Imai H, Komine K, Ouchi K, Taniguchi S, Yoshida Y, Numakura R, Ishikawa S, Shirakawa T, Saito R, Ishioka C, Kawakami H
Fam Cancer · 2026 Feb · PMID 41632335 · Publisher ↗
Li-Fraumeni syndrome (LFS) is a hereditary cancer-predisposing disorder caused by germline pathogenic variants in the TP53 gene. Attenuated LFS represents a clinically milder form characterized by lower penetrance and la...
Li-Fraumeni syndrome (LFS) is a hereditary cancer-predisposing disorder caused by germline pathogenic variants in the TP53 gene. Attenuated LFS represents a clinically milder form characterized by lower penetrance and later tumor onset, evading standard diagnostic criteria. We report a case of a 36-year-old Japanese woman who presented with hematochezia and was diagnosed with metastatic rectal adenocarcinoma. After failure of the first- to third-line chemotherapies, plasma-based comprehensive genomic profiling (CGP) was performed. The assay revealed a TP53 p.R181H variant (allele frequency: 0.512), KRAS p.G12D variant, PIK3CA p.E545K variant, and a CTNNB1 splicing variant. Family history included multiple gastrointestinal and hematological malignancies in first- and second-degree relatives. Germline testing confirmed heterozygosity of TP53 p.R181H, a temperature-sensitive variant suggested to have reduced penetrance. Notably, this variant is relatively common in European populations but rare in East Asian cohorts. To the best of our knowledge, this is the first reported East Asian case of attenuated LFS associated with the TP53 p.R181H variant. This case underscores the broader phenotypic spectrum of LFS. With the growing use of CGP, LFS may be identified more frequently in East Asia, potentially revealing attenuated LFS missed by traditional diagnostic criteria.
Hereditary ovarian cancer in women with African ancestry: a scoping review.
Rossouw B, Araujo M, Krause A … +1 more , Baine-Savanhu F
Fam Cancer · 2026 Jan · PMID 41619087 · Full text
This scoping review explored genetic variants associated with hereditary ovarian cancer in women of African ancestry. Around 20% of ovarian cancers are hereditary, with BRCA1 and BRCA2 variants accounting for 20–55% of t...
This scoping review explored genetic variants associated with hereditary ovarian cancer in women of African ancestry. Around 20% of ovarian cancers are hereditary, with BRCA1 and BRCA2 variants accounting for 20–55% of these cases, while other implicated genes include BRIP1, ATM, RAD51C, RAD51D, and the Lynch syndrome genes. The genetic basis of ovarian cancer in women of African ancestry, however, remains poorly understood. Accurate diagnosis of hereditary cancer syndromes is crucial given their personal and familial implications, informing patient management, surveillance, and cascade testing for at-risk relatives. Eligible studies included women of African ancestry with confirmed primary ovarian, peritoneal, or fallopian tube cancer who underwent germline genetic testing for hereditary cancer syndromes. Studies based solely on somatic testing or genome-wide association approaches were excluded. A comprehensive search of PubMed, Scopus, Web of Science, Google Scholar, and ProQuest Dissertations and Theses Global was conducted. Two reviewers independently screened citations and extracted data using a standardized form, and results were summarised narratively and in tables according to JBI scoping review guidelines. Thirty studies were included, primarily involving African American and North African participants. Only four focused specifically on hereditary ovarian cancer; the remainder primarily examined breast cancer cohorts with some ovarian cancer cases. Across these studies, 75 pathogenic variants were identified in 110 families, with 92% in BRCA1 or BRCA2. Research on hereditary ovarian cancer in women with African ancestry remains extremely limited, highlighting the urgent need for broader next-generation sequencing studies to inform clinical care.
A history of the collaborative group of the Americas on inherited gastrointestinal cancer (CGA-IGC): 1995-2025.
Dudley B, Boman BM, Greenblatt MS … +17 more , Erdman SH, Wise PE, Brand RE, Burke CA, Guillem JG, Hall MJ, Hampel H, Heald B, Kalady MF, Katona BW, Kupfer SS, Lynch PM, Patel SG, Stanich PP, Stoffel EM, Yurgelun MB, Church J
Fam Cancer · 2026 Jan · PMID 41619078 · Publisher ↗
The Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) was created in 1995, when a small group of clinicians and researchers interested in improving the understanding of hereditary gastroi...
The Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) was created in 1995, when a small group of clinicians and researchers interested in improving the understanding of hereditary gastrointestinal (GI) cancer syndromes met in St. Louis. The organization was modeled after similar societies being formed internationally, with the goals of addressing uniquely American aspects of the healthcare of patients, providing opportunities for interested institutions and individuals to collaborate on studies, and facilitating affordable and accessible meetings. Over the subsequent 30 years, CGA-IGC has grown in size and scope. The organization was formally established in 1996 and annual academic meetings began in 1997, at which time the organization's name was the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC). Milestones included the organization's first strategic plan in 2010, the hiring of outside administrative management in 2014, and the creation of working committees in 2017. These decisions led to progressive growth of the organization, allowing for provision of year-round educational opportunities and increased member engagement. Given the recognition that the hereditary syndromes of interest to this group involve all parts of the gastrointestinal tract, the organization's name was changed from Collaborative Group of the Americas on Inherited Colorectal Cancer to Collaborative Group of the Americas on Inherited Gastrointestinal Cancer in 2018. Presently, CGA-IGC enjoys record-high membership, with over 500 members. A new 3-year strategic plan was implemented in 2024 to guide CGA-IGC into its next 30 years.
Germline MLH1 c.-42 C > T is a likely pathogenic variant predisposing to a reduced-penetrance/modified Lynch syndrome phenotype featuring MLH1-methylated cancers.
Buchanan DD, Alvarez R, Mahmood K … +18 more , Clendenning M, Georgeson P, Walker R, Como J, Preston SG, Joseland S, Mohammadsaeedi K, Aguirre F, Zhou L, Hazelett DJ, Jenkins MA, Rosty C, Winship IM, Macrae FA, Dwarte TM, Nixon D, Hitchins MP, Joo JE
Fam Cancer · 2026 Jan · PMID 41619042 · Full text
The germline MLH1 c.-42 C > T (rs41285097) promoter variant has been identified in cases with MLH1-deficient colorectal or endometrial cancers but remains a variant of uncertain significance. Genetic testing identified t...
The germline MLH1 c.-42 C > T (rs41285097) promoter variant has been identified in cases with MLH1-deficient colorectal or endometrial cancers but remains a variant of uncertain significance. Genetic testing identified two new MLH1 c.-42 C > T index cases from Australia and the USA. Clinicopathologic and molecular characterisation of tumour and non-neoplastic tissues was performed to investigate the potential mechanism of pathogenesis of this variant. The male Australian proband developed MLH1-deficient, BRAF p.V600 wildtype, CIMP-negative colon cancer at 61 years. MLH1 monoallelic methylation and a somatic pathogenic mutation, MLH1 c.1122_1126dup p.Asp376Valfs*27, were identified in his tumour. Droplet digital PCR (ddPCR) detected mosaic MLH1 methylation in normal colonic mucosa adjacent to the cancer (3.7%) with lower levels in blood (0.07%) and saliva (0.09%). The USA proband developed MLH1-deficient endometrial cancer at 38 years with MLH1 monoallelic methylation and loss-of-heterozygosity of the wildtype c.-42 C allele. No evidence of MLH1 methylation was found by ddPCR in normal tissues. MLH1 c.-42 C > T heterozygous relatives from both families had either no or extremely low levels of MLH1 methylation within blood or saliva. Allelic expression from MLH1 c.-42T was reduced to 70% relative to the wild-type allele in saliva from three heterozygotes. Three additional pedigrees were identified from the Colon Cancer Family Registry. Evaluation of combined multifactorial data from pooled informative index cases supports reclassification of this variant as “likely pathogenic” according to current ACMG/AMP mismatch repair gene-specific guidelines, though with likely reduced penetrance and/or modified phenotype. These findings highlight the clinical importance of identifying MLH1 c.-42 C > T to inform cancer risk management.
Hearing preservation and restoration surgery in NF2-related schwannomatosis.
Wood CG, Huey N, Carter C … +4 more , Truong N, Ii Barker FG, Plotkin SR, Welling DB
Fam Cancer · 2026 Jan · PMID 41618020 · Publisher ↗
To analyze factors associated with hearing preservation in patients undergoing surgery with NF2-related schwannomatosis (NF2-SWN) vestibular schwannomas (VS), and to evaluate artificial intelligence/machine learning (AI/...
To analyze factors associated with hearing preservation in patients undergoing surgery with NF2-related schwannomatosis (NF2-SWN) vestibular schwannomas (VS), and to evaluate artificial intelligence/machine learning (AI/ML) predictors of hearing preservation. Retrospective analysis of NF2-SWN patients with a preoperative word recognition score (WRS) of greater than 50% who were undergoing surgical resection of VS with the goal of hearing preservation. Factors evaluated for influence on hearing preservation included preoperative tumor size and location, pure tone average and WRS, age of onset of NF2-SWN symptoms, auditory brainstem response (ABR), NF2 genetic severity score, inflammation in the cochlea and labyrinth, and surgical approach. The relationship between factors and hearing preservation was evaluated with univariate and multivariable analysis and a “SuperLearner” AI/ML model. When hearing was not preserved, outcomes of cochlear implants (CI) and auditory brainstem implants (ABI) are presented. Of 322 patients with NF2-SWN, 191 underwent surgical excision of VS. Fifty-two (27%) had WRS > 50% and tumor configuration allowing attempted hearing preservation. Twenty-three of the 52 patients had postoperative WRS > 50% (44%). The mean tumor size when hearing was preserved was 16.4 mm whereas the mean tumor size in those not preserved was 22.2 mm giving an odds ratio (OR) on univariate analysis of 0.90 (CI 0.85–0.95) suggesting larger tumors were less likely to have preserved hearing. For 12 patients with greater than 5-year follow up and preserved hearing, the mean time for their WRS to degrade below 50% was 11.6 years. Univariate regression also identified the presence of normal wave V on ABR having higher OR of hearing preservation 30.9 (95% CI, 3.78, 252.2) whereas tumors touching the brainstem lowered the odds ratio of hearing preservation of 0.07 (95%CI, 0.02, 0.24). However, none of the factors remained significant on multivariate regression after adjusting for other factors. In an AI/ML SuperLearner model, the most influential variables were normal ABR, lack of tumor contact with the brainstem, and preoperative WRS. The accuracy was 85% (79–91%); the sensitivity: 0.69 (0.50–0.86) and the specificity: 0.87 (0.80–0.95). This model of implies that collectively there is indeed useful information for predicting hearing preservation at surgery from these data. Cochlear implant and auditory brainstem implant rehabilitation is also reported. Seventy-three percent of NF2-SWN patients in this study had poor hearing at the time of surgery limiting hearing preservation. Current hearing preservation options are largely inadequate. Factors influencing postoperative hearing in NF2-SWN VS resection when combined with AI/ML may aid in predicting surgical outcomes. Further confirmational studies are needed. CI and ABI are shown to provide long-term hearing rehabilitation options for a modest proportion of NF2-SWN patients. Earlier intervention and better treatment options are needed.
Exploration of familial genetic test result communication among Black women within an academic safety net hospital.
Aluwalia R, Ali N, Stanislaw C … +3 more , Leonis R, Jones J, Paysour J
Fam Cancer · 2026 Jan · PMID 41615528 · Publisher ↗
Individuals who receive a pathogenic result from hereditary cancer genetic testing face challenges effectively sharing this information with their relatives, leading to low rates of familial cascade testing. Communicatio...
Individuals who receive a pathogenic result from hereditary cancer genetic testing face challenges effectively sharing this information with their relatives, leading to low rates of familial cascade testing. Communication of a cancer predisposition and subsequent familial testing is important, so at-risk relatives can receive appropriate medical screenings and risk-reducing interventions. While barriers and facilitators to cascade testing have been explored primarily among individuals who are White and report higher incomes, they have not been thoroughly assessed among other groups. This study explored the experiences of Black women sharing their pathogenic cancer genetic test results with their relatives. All eight participants had received genetic counseling and testing at Grady Memorial Hospital, an academic safety net hospital in Atlanta, Georgia. Participants completed semi-structured interviews about barriers and facilitators they experienced while disclosing their genetic test results to relatives. Interviews were independently coded amongst two coders (RA/JP), thematic content analysis was performed, and a pooled Cohen’s Kappa of 0.69 was obtained. Notable barriers to disclosure included distrust in the accuracy of genetic testing results and misconceptions such as perm products causing heritable gene mutations. Unique facilitators of cascade testing include feelings of empowerment and reliance on personal faith as a coping strategy before sharing results. Participants provided suggestions to improve the cascade testing process, such as family result sessions and community awareness events. Genetic counselors can utilize these unique facilitators and barriers to cascade testing to provide culturally appropriate care and to improve communication of results among families receiving hereditary cancer testing.
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