Familial Cancer最新文献

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.

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.

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.

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.

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.