Familial Cancer最新文献

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.

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.

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.

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.