Familial Cancer最新文献

{"title":"The best linear unbiased prediction (BLUP) method as a tool to estimate the lifetime risk of pancreatic ductal adenocarcinoma in high-risk individuals with no known pathogenic germline variants.","authors":"Cristina-Marianini-Rios, María E Castillo Sanchez, Ana García García de Paredes, Mercedes Rodríguez, Emma Barreto, Jorge Villalón López, Raquel Fuentes, María Muñoz Beltrán, Alfonso Sanjuanbenito, Eduardo Lobo, Alejandra Caminoa, Ignacio Ruz-Caracuel, Sergio López Durán, José Ramón Foruny Olcina, Javier Blázquez, Enrique Vázquez Sequeros, Alfredo Carrato, Jose Carlos Martínez Ávila, Julie Earl","doi":"10.1007/s10689-024-00397-w","DOIUrl":"10.1007/s10689-024-00397-w","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown. Surveillance of high-risk individuals (HRI) from these families by imaging aims to detect PDAC at an early stage to improve prognosis. However, the genetic basis is unknown in the majority of HRIs, with only around 10-13% of families carrying known pathogenic germline mutations. The aim of this study was to assess an individual's genetic cancer risk based on sex and personal and family history of cancer. The Best Linear Unbiased Prediction (BLUP) methodology was used to estimate an individual's predicted risk of developing cancer during their lifetime. The model uses different demographic factors in order to estimate heritability. A reliable estimation of heritability for pancreatic cancer of 0.27 on the liability scale, and 0.07 at the observed data scale as obtained, which is different from zero, indicating a polygenic inheritance pattern of PDAC. BLUP was able to correctly discriminate PDAC cases from healthy individuals and those with other cancer types. Thus, providing an additional tool to assess PDAC risk HRI with an assumed genetic predisposition in the absence of known pathogenic germline mutations.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"233-246"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081164","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":"The Spanish Familial Pancreatic Cancer Registry (PANGENFAM): a decade follow-up of individuals at high-risk for pancreatic cancer.","authors":"Julie Earl, Raquel Fuentes, María E Castillo Sanchez, Ana García García de Paredes, María Muñoz, Alfonso Sanjuanbenito, Eduardo Lobo, Alejandra Caminoa, Mercedes Rodríguez, Emma Barreto, Jorge Villalón López, Ignacio Ruz-Caracuel, Sergio López Durán, José Ramón Foruny Olcina, Bárbara Luna Sánchez, Sonia Camaño Páez, Ana Torres, Javier Blázquez, Enrique Vázquez Sequeros, Alfredo Carrato","doi":"10.1007/s10689-024-00388-x","DOIUrl":"10.1007/s10689-024-00388-x","url":null,"abstract":"<p><p>The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29-83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"383-392"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944744","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":"Expanding access to genetic testing for pancreatic cancer.","authors":"Nicolette Juliana Rodriguez, Sapna Syngal","doi":"10.1007/s10689-024-00389-w","DOIUrl":"10.1007/s10689-024-00389-w","url":null,"abstract":"<p><p>Among individuals with pancreatic ductal adenocarcinoma (PDAC) 5-10% have a pathogenic germline variant (PGV) in a PDAC susceptibility gene. Guidelines recommend genetic testing among all individuals with PDAC. Additionally, at-risk relatives of PDAC patients benefit from their own genetic education, risk assessment, and testing. Multigene panel testing (MGPT) can identify individuals with inherited cancer risk who can benefit from early cancer surveillance and risk reduction strategies. This manuscript discusses various healthcare delivery models for MGPT including traditional in-person genetic counseling, novel integrated in-person infrastructures, telemedicine genetics care via telephone- or video-visits and direct-to-consumer testing. Barriers and facilitators to care on the individual, provider, and system level are also outlined including specific considerations for historically marginalized communities.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"247-254"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908290","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":"Can our experience with surveillance for inherited pancreatic cancer help to identify early pancreatic cancer in the general population?","authors":"J-Matthias Löhr, Daniel Öhlund, Emma Söreskog, Emil Andersson, Miroslav Vujasinovic, Niklas Zethraeus, Malin Sund","doi":"10.1007/s10689-024-00363-6","DOIUrl":"10.1007/s10689-024-00363-6","url":null,"abstract":"<p><p>Screening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate tests.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"399-403"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027745","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":"Colonoscopic surveillance in Lynch syndrome: guidelines in perspective","authors":"Joaquín Castillo-Iturra, Ariadna Sánchez, Francesc Balaguer","doi":"10.1007/s10689-024-00414-y","DOIUrl":"https://doi.org/10.1007/s10689-024-00414-y","url":null,"abstract":"<p>Lynch syndrome predisposes to a high risk of colorectal cancer and colonoscopy remains the primary preventive strategy. The prevention of colorectal cancer through colonoscopy relies on identifying and removing adenomas, the main precursor lesion. Nevertheless, colonoscopy is not an optimal strategy since post-colonoscopy colorectal cancer remains an important issue. In continuation of a 2021 journal review, the present article seeks to offer an updated perspective by examining relevant articles from the past 3 years. We place recent findings in the context of existing guidelines, with a specific focus on colonoscopy surveillance. Key aspects explored include colonoscopy quality standards, timing of initiation, and surveillance intervals. Our review provides a comprehensive analysis of adenoma-related insights in Lynch syndrome, delving into emerging technologies like virtual chromoendoscopy and artificial intelligence-assisted endoscopy. This review aims to contribute valuable insights into the topic of colonoscopy surveillance in Lynch syndrome.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"133 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778121","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":"In memoriam: Gloria Petersen, PhD (1950-2023).","authors":"Hans Vasen","doi":"10.1007/s10689-024-00406-y","DOIUrl":"https://doi.org/10.1007/s10689-024-00406-y","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316964","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":"Editorial for familial cancer: cascade genetic testing.","authors":"Maria Katapodi, Joanne Ngeow, Yuen Yie, Melissa Frey","doi":"10.1007/s10689-024-00378-z","DOIUrl":"10.1007/s10689-024-00378-z","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"109-110"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335258","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":"Cascade genetic testing for hereditary cancer syndromes: a review of barriers and breakthroughs.","authors":"Rachel Levine, Ryan M Kahn, Luiza Perez, Jesse Brewer, Samantha Ratner, Xuan Li, Effi Yeoshoua, Melissa K Frey","doi":"10.1007/s10689-024-00373-4","DOIUrl":"10.1007/s10689-024-00373-4","url":null,"abstract":"<p><p>Germline genetic sequencing is now at the forefront of cancer treatment and preventative medicine. Cascade genetic testing, or the testing of at-risk relatives, is extremely promising as it offers genetic testing and potentially life-saving risk-reduction strategies to a population exponentially enriched for the risk of carrying a cancer-associated pathogenic variant. However, many relatives do not complete cascade testing due to barriers that span individual, relationship, healthcare community, and societal/policy domains. We have reviewed the published research on cascade testing. Our aim is to evaluate barriers to cascade genetic testing for hereditary cancer syndromes and explore strategies to mitigate these barriers, with the goal of promoting increased uptake of cascade genetic testing.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"111-120"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293271","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":"Cascade screening in HBOC and Lynch syndrome: guidelines and procedures in a UK centre.","authors":"D Gareth Evans, Kate Green, George J Burghel, Claire Forde, Fiona Lalloo, Helene Schlecht, Emma R Woodward","doi":"10.1007/s10689-024-00360-9","DOIUrl":"10.1007/s10689-024-00360-9","url":null,"abstract":"<p><p>In the 33 years since the first diagnostic cancer predisposition gene (CPG) tests in the Manchester Centre for Genomic Medicine, there has been substantial changes in the identification of index cases and cascade testing for at-risk family members. National guidelines in England and Wales are usually determined from the National Institute of healthcare Evidence and these have impacted on the thresholds for testing BRCA1/2 in Hereditary Breast Ovarian Cancer (HBOC) and in determining that all cases of colorectal and endometrial cancer should undergo screening for Lynch syndrome. Gaps for testing other CPGs relevant to HBOC have been filled by the UK Cancer Genetics Group and CanGene-CanVar project (web ref. https://www.cangene-canvaruk.org/ ). We present time trends (1990-2020) of identification of index cases with germline CPG variants and numbers of subsequent cascade tests, for BRCA1, BRCA2, and the Lynch genes (MLH1, MSH2, MSH6 and PMS2). For BRCA1/2 there was a definite increase in the proportion of index cases with ovarian cancer only and pre-symptomatic index tests both doubling from 16 to 32% and 3.2 to > 8% respectively. A mean of 1.73-1.74 additional family tests were generated for each BRCA1/2 index case within 2 years. Overall close to one positive cascade test was generated per index case resulting in > 1000 risk reducing surgery operations. In Lynch syndrome slightly more cascade tests were performed in the first two years potentially reflecting the increased actionability in males with 42.2% of pre-symptomatic tests in males compared to 25.8% in BRCA1/2 (p < 0.0001).</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"187-195"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119228","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":"Challenges and opportunities for Lynch syndrome cascade testing in the United States.","authors":"Lauren E Passero, Megan C Roberts","doi":"10.1007/s10689-024-00374-3","DOIUrl":"10.1007/s10689-024-00374-3","url":null,"abstract":"<p><p>Lynch syndrome is an underdiagnosed genetic condition that increases lifetime colorectal, endometrial, and other cancer risk. Cascade testing in relatives is recommended to increase diagnoses and enable access to cancer prevention services, yet uptake is limited due to documented multi-level barriers. Individual barriers such as feelings of fear, guilt, and anxiety and limited knowledge about Lynch syndrome as well as interpersonal barriers including complex family dynamics and language barriers limit family communication about Lynch syndrome and prevent uptake of genetic screening for relatives. Organizational and environmental barriers including a shortage of genetics professionals, high costs, and fears of discrimination also reduce cascade testing. These multi-level barriers may disproportionately impact underserved populations in the United States, such as individuals with lower incomes, limited English-speaking proficiency, lower educational attainment, and inadequate access to health systems. Multi-level facilitators of cascade testing include interpersonal support from family members, peers, and healthcare providers, educational resources, and motivation to improve family health. Taken together, these barriers and facilitators demonstrate a need for interventions and strategies that address multi-level factors to increase cascade testing in families with Lynch syndrome and other hereditary cancer conditions. We provide an example of a cascade testing intervention that has been developed for use in individuals diagnosed with Lynch syndrome and discuss the variety of current approaches to addressing these multi-level barriers.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"147-154"},"PeriodicalIF":1.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318139","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}