Familial Cancer最新文献

{"title":"Pilot study of a decision aid on BRCA1/2 genetic testing among Orthodox Jewish women","authors":"Meghna S. Trivedi, Haley Manley, Haeseung Yi, Thomas Silverman, Wendy K. Chung, Paul S. Appelbaum, Rebecca Starck, Isaac Schecter, Rita Kukafka, Katherine D. Crew","doi":"10.1007/s10689-024-00371-6","DOIUrl":"https://doi.org/10.1007/s10689-024-00371-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Orthodox Jewish women face unique social, cultural, and religious factors that may influence uptake of <i>BRCA1/2</i> genetic testing. We examined the impact of a web-based decision aid (DA) on <i>BRCA1/2</i> genetic testing intention/completion among Orthodox Jewish women. We conducted a single-arm pilot study among 50 Orthodox Jewish women who were given access to a web-based DA entitled <i>RealRisks</i> and administered serial surveys at baseline and 1 and 6 months after exposure to the DA. Descriptive statistics were conducted for baseline characteristics and study measures. Comparisons were made to assess changes in study measures over time. Fifty Orthodox Jewish women enrolled in the study with a mean age of 43.9 years (standard deviation [SD] 14.6), 70% Modern Orthodox, 2% with personal history of breast cancer, and 68% and 16% with a family history of breast or ovarian cancer, respectively. At baseline, 27 (54%) participants intended to complete genetic testing. Forty-three participants (86%) completed <i>RealRisks</i> and the 1-month survey and 38 (76%) completed the 6-month survey. There was a significant improvement in <i>BRCA1/2</i> genetic testing knowledge and decrease in decisional conflict after exposure to the DA. At 1 month, only 20 (46.5%) completed or intended to complete genetic testing (<i>p</i> = 0.473 compared to baseline). While the DA improved genetic testing knowledge and reduced decisional conflict, genetic testing intention/completion did not increase over time. Future interventions should directly address barriers to <i>BRCA1/2</i> genetic testing uptake and include input from leaders in the Orthodox Jewish community.</p><h3 data-test=\"abstract-sub-heading\">ClinicalTrials.gov ID</h3><p>NCT03624088 (8/7/18).</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"107 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575664","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":"Understanding familial risk of pancreatic ductal adenocarcinoma","authors":"Raymond M. Paranal, Laura D. Wood, Alison P. Klein, Nicholas J. Roberts","doi":"10.1007/s10689-024-00383-2","DOIUrl":"https://doi.org/10.1007/s10689-024-00383-2","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is the result of an accumulation of sequential genetic alterations. These genetic alterations can either be inherited, such as pathogenic germline variants that are associated with an increased risk of cancer, or acquired, such as somatic mutations that occur during the lifetime of an individual. Understanding the genetic basis of inherited risk of PDAC is essential to advancing patient care and outcomes through improved clinical surveillance, early detection initiatives, and targeted therapies. In this review we discuss factors associated with an increased risk of PDAC, the prevalence of genetic variants associated with an increased risk in patients with PDAC, estimates of PDAC risk in carriers of pathogenic germline variants in genes associated with an increased risk of PDAC. The role of common variants in pancreatic cancer risk will also be discussed.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"164 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590033","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":"Genetic and other risk factors for pancreatic ductal adenocarcinoma (PDAC)","authors":"Michelle F. Jacobs, Elena M. Stoffel","doi":"10.1007/s10689-024-00372-5","DOIUrl":"https://doi.org/10.1007/s10689-024-00372-5","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in poor prognosis and low 5-year survival rates. While early evidence suggests increased long-term survival in those with screen-detected resectable cancers, surveillance imaging is currently only recommended for individuals with a lifetime risk of PDAC ≥ 5%. Identification of risk factors for PDAC provides opportunities for early detection, risk reducing interventions, and targeted therapies, thus potentially improving patient outcomes. Here, we summarize modifiable and non-modifiable risk factors for PDAC. We review hereditary cancer syndromes associated with risk for PDAC and their implications for patients and their relatives. In addition, other biologically relevant pathways and environmental and lifestyle risk factors are discussed. Future work may focus on elucidating additional genetic, environmental, and lifestyle risk factors that may modify PDAC risk to continue to identify individuals at increased risk for PDAC who may benefit from surveillance and risk reducing interventions.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"40 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590020","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":"The role of endoscopic ultrasound in the detection of pancreatic lesions in high-risk individuals","authors":"Kasper A. Overbeek, Djuna L. Cahen, Marco J. Bruno","doi":"10.1007/s10689-024-00380-5","DOIUrl":"https://doi.org/10.1007/s10689-024-00380-5","url":null,"abstract":"<p>Individuals at high risk of developing pancreatic ductal adenocarcinoma are eligible for surveillance within research programs. These programs employ periodic imaging in the form of magnetic resonance imaging/magnetic resonance cholangiopancreatography or endoscopic ultrasound for the detection of early cancer or high-grade precursor lesions. This narrative review discusses the role of endoscopic ultrasound within these surveillance programs. It details its overall strengths and limitations, yield, burden on patients, and how it compares to magnetic resonance imaging. Finally, recommendations are given when and how to incorporate endoscopic ultrasound in the surveillance of high-risk individuals.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"62 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140590132","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: Steffen Bülow (1943-2023).","authors":"Hans F A Vasen","doi":"10.1007/s10689-024-00358-3","DOIUrl":"https://doi.org/10.1007/s10689-024-00358-3","url":null,"abstract":"","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119229","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":"Li Fraumeni Syndrome predisposes to gastro-esophageal junction tumours.","authors":"Douglas Tjandra, Alex Boussioutas","doi":"10.1007/s10689-023-00353-0","DOIUrl":"10.1007/s10689-023-00353-0","url":null,"abstract":"<p><p>Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"29-33"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416779","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":"Functional and phenotypic consequences of an unusual inversion in MSH2.","authors":"Dylan Pelletier, Abhijit Rath, Nelly Sabbaghian, Manuela Pelmus, Catherine Hudon, Karine Jacob, Leora Witowski, Avi Saskin, Christopher D Heinen, William D Foulkes","doi":"10.1007/s10689-023-00350-3","DOIUrl":"10.1007/s10689-023-00350-3","url":null,"abstract":"<p><p>Lynch syndrome is an autosomal dominant disorder that usually results from a pathogenic germline variant in one of four genes (MSH2, MSH6, MLH1, PMS2) involved in DNA mismatch repair. Carriers of such variants are at risk of developing numerous cancers during adulthood. Here we report on a family suspected of having Lynch syndrome due to a history of endometrial adenocarcinoma, ovarian clear cell carcinoma, and adenocarcinoma of the duodenum in whom we identified a germline 29 nucleotide in-frame inversion in exon 3 of MSH2. We further show that this variant is almost completely absent at the protein level, and that the associated cancers have complete loss of MSH2 and MSH6 expression by immunohistochemistry. Functional investigation of this inversion in a laboratory setting revealed a resultant abnormal protein function. Thus, we have identified an unusual, small germline inversion in a mismatch repair gene that does not lead to a premature stop codon yet appears likely to be causal for the observed cancers.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"1-7"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153425","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":"Low prevalence of gastric intestinal metaplasia and Helicobacter pylori on surveillance upper endoscopy in Lynch syndrome.","authors":"Marya Pulaski, Michaela Dungan, Marina Weber, Gillain Constantino, Bryson W Katona","doi":"10.1007/s10689-023-00354-z","DOIUrl":"10.1007/s10689-023-00354-z","url":null,"abstract":"<p><p>Lynch syndrome (LS) increases the risk of numerous different cancers including gastric cancer. While some current guidelines recommend empiric gastric biopsies be performed during upper gastrointestinal cancer surveillance in Lynch syndrome (LS), the yield of these biopsies and the prevalence of gastric intestinal metaplasia (GIM) and Helicobacter pylori (HP) in LS remains unknown. Herein we analyze 165 consecutive individuals with LS who underwent upper endoscopic surveillance with biopsies of the gastric antrum and body being performed universally in all individuals. Of the study cohort, 6.7% of universally biopsied individuals with LS had GIM and/or HP (5.5% GIM, 3.6% HP). Biopsies of the gastric body did not increase rates of GIM/HP identification compared to antral biopsies alone. GIM was detected on subsequent surveillance in 2.2% of individuals without prior GIM, which may represent either newly developed GIM or GIM that was missed on a prior upper endoscopy due to sampling error. These findings support inclusion of at least baseline gastric antrum biopsies as a routine component of all standard surveillance upper endoscopies performed in LS.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"23-27"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641986","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":"Breast density in NF1 women: a retrospective study.","authors":"R De Santis, G Cagnoli, B Rinaldi, D Consonni, Beatrice Conti, M Eoli, A Liguori, M Cosentino, G Carrafiello, O Garrone, M Giroda, C Cesaretti, M S Sfondrini, D Gambini, F Natacci","doi":"10.1007/s10689-023-00355-y","DOIUrl":"10.1007/s10689-023-00355-y","url":null,"abstract":"<p><p>Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were compared with those from 300 healthy subjects to verify differences in breast density. Mammograms were independently reviewed and scored by a radiologist and using a Computer-Aided Detection (CAD) software. The comparison of breast density between NF1 patients and controls was performed through Chi-squared test and with multivariable ordinal logistic models adjusted for age, body mass index (BMI), number of pregnancies, and menopausal status.breast density was influenced by BMI and menopausal status in both NF1 patients and healthy subjects. No difference in breast density was observed between NF1 patients and the healthy female population, even after considering the potential confounding factors.Although NF1 and a highly fibroglandular breast are known risk factors of BC, in this study, NF1 patients were shown to have comparable breast density to healthy subjects. The presence of pathogenic variants in the NF1 gene does not influence the breast density value.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":" ","pages":"35-40"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546170","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":"Inherited BRCA1 and RNF43 pathogenic variants in a familial colorectal cancer type X family","authors":"James M. Chan, Mark Clendenning, Sharelle Joseland, Peter Georgeson, Khalid Mahmood, Jihoon E. Joo, Romy Walker, Julia Como, Susan Preston, Shuyi Marci Chai, Yen Lin Chu, Aaron L. Meyers, Bernard J. Pope, David Duggan, J. Lynn Fink, Finlay A. Macrae, Christophe Rosty, Ingrid M. Winship, Mark A. Jenkins, Daniel D. Buchanan","doi":"10.1007/s10689-023-00351-2","DOIUrl":"https://doi.org/10.1007/s10689-023-00351-2","url":null,"abstract":"<p>Genetic susceptibility to familial colorectal cancer (CRC), including for individuals classified as Familial Colorectal Cancer Type X (FCCTX), remains poorly understood. We describe a multi-generation CRC-affected family segregating pathogenic variants in both <i>BRCA1</i>, a gene associated with breast and ovarian cancer and <i>RNF43</i>, a gene associated with Serrated Polyposis Syndrome (SPS). A single family out of 105 families meeting the criteria for FCCTX (Amsterdam I family history criteria with mismatch repair (MMR)-proficient CRCs) recruited to the Australasian Colorectal Cancer Family Registry (ACCFR; 1998–2008) that underwent whole exome sequencing (WES), was selected for further testing. CRC and polyp tissue from four carriers were molecularly characterized including a single CRC that underwent WES to determine tumor mutational signatures and loss of heterozygosity (LOH) events. Ten carriers of a germline pathogenic variant <i>BRCA1</i>:c.2681_2682delAA p.Lys894ThrfsTer8 and eight carriers of a germline pathogenic variant <i>RNF43</i>:c.988 C &gt; T p.Arg330Ter were identified in this family. Seven members carried both variants, four of which developed CRC. A single carrier of the <i>RNF43</i> variant met the 2019 World Health Organization (WHO²⁰¹⁹) criteria for SPS, developing a <i>BRAF</i> p.V600 wildtype CRC. Loss of the wildtype allele for both <i>BRCA1</i> and <i>RNF43</i> variants was observed in three CRC tumors while a LOH event across chromosome 17q encompassing both genes was observed in a CRC. Tumor mutational signature analysis identified the homologous recombination deficiency (HRD)-associated COSMIC signatures SBS3 and ID6 in a CRC for a carrier of both variants. Our findings show digenic inheritance of pathogenic variants in <i>BRCA1</i> and <i>RNF43</i> segregating with CRC in a FCCTX family. LOH and evidence of BRCA1-associated HRD supports the importance of both these tumor suppressor genes in CRC tumorigenesis.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"9 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138554054","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}