Hereditary Cancer in Clinical Practice最新文献

{"title":"Germline mutations among Polish patients with acute myeloid leukemia.","authors":"Aneta Bąk,&nbsp;Katarzyna Skonieczka,&nbsp;Anna Jaśkowiec,&nbsp;Anna Junkiert-Czarnecka,&nbsp;Marta Heise,&nbsp;Maria Pilarska-Deltow,&nbsp;Stanisław Potoczek,&nbsp;Maria Czyżewska,&nbsp;Olga Haus","doi":"10.1186/s13053-021-00200-2","DOIUrl":"https://doi.org/10.1186/s13053-021-00200-2","url":null,"abstract":"<p><strong>Background: </strong>A small but important proportion of patients (4-10 %) with AML have germline mutations. They can cause the development of AML at an earlier age, confer a higher risk of relapse or predispose to secondary leukemias, including therapy-related leukemias. The analysis of germline mutations in a patient and his/her family is also critical for the selection of suitable family donors if the patient is a candidate for hematopoietic stem cell transplantation (HSCT).</p><p><strong>Methods: </strong>103 unrelated consecutive patients with de novo AML were enrolled in the study. Control group consisted of 103 persons from the general population. We performed NGS sequencing of bone marrow cells and buccal swabs DNA of six genes: CEBPA, DDX41, ETV6, TERT, GATA2, and IDH2 to detect germline pathogenic mutations.</p><p><strong>Results: </strong>In the investigated group, 49 variants were detected in six genes. 26 of them were somatic and 23 germline. Germline variants were detected in all six tested genes. Eight pathogenic germline mutations were detected in 7 AML patients, in three genes: CEBPA, ETV6, and IDH2. One patient had two pathogenic germinal mutations, one in ETV6 and one in CEBPA gene. We identified one novel pathogenic germline mutation in CEBPA gene. The difference in frequency of all pathogenic germline mutations between the tested (7.77 %) and control groups (0.97 %) was statistically significant (p = 0.046). In the tested group, the median age at AML diagnosis was 11 years lower in patients with pathogenic germline mutations than in patients without them (p = 0.028).</p><p><strong>Conclusions: </strong>We showed higher frequency of CEBPA, ETV6, and IDH2 germline mutations in AML patients than in control group, which confirms the role of these mutations in the development of AML. We also showed that the median age at the onset of AML in patients with pathogenic germline mutations is significantly lower than in patients without them.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"42"},"PeriodicalIF":1.7,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39512031","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":"Danish guidelines for management of non-APC-associated hereditary polyposis syndromes.","authors":"Anne Marie Jelsig,&nbsp;John Gásdal Karstensen,&nbsp;Niels Jespersen,&nbsp;Zohreh Ketabi,&nbsp;Charlotte Lautrup,&nbsp;Karina Rønlund,&nbsp;Lone Sunde,&nbsp;Karin Wadt,&nbsp;Ole Thorlacius-Ussing,&nbsp;Niels Qvist","doi":"10.1186/s13053-021-00197-8","DOIUrl":"https://doi.org/10.1186/s13053-021-00197-8","url":null,"abstract":"<p><p>Hereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes.. The diagnosis entails surveillance from an early age, but universal guideline on how to manage and surveille these new syndromes are lacking. This paper represents a condensed version of the recent guideline (2020) from a working group appointed by the Danish Society of Medical Genetics and the Danish Society of Surgery on recommendations for the surveillance of patients with hereditary polyposis syndromes, including rare polyposis syndromes.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"41"},"PeriodicalIF":1.7,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39494203","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":"Risk reduction strategies for BRCA1/2 hereditary ovarian cancer syndromes: a clinical practice guideline.","authors":"Michelle Jacobson, Nadia Coakley, Marcus Bernardini, Kelly-Ann Branco, Laurie Elit, Sarah Ferguson, Raymond Kim","doi":"10.1186/s13053-021-00196-9","DOIUrl":"10.1186/s13053-021-00196-9","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this guideline is to make recommendations regarding the care of women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2.</p><p><strong>Methods: </strong>Draft recommendations were formulated based on evidence obtained through a systematic review of RCTs, comparative retrospective studies and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners.</p><p><strong>Results: </strong>The literature search yielded 1 guideline, 5 systematic reviews, and 15 studies that met the eligibility criteria.</p><p><strong>Conclusions: </strong>In women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2 screening for ovarian cancer is not recommended. Risk-reducing surgery is recommended to reduce the risk of ovarian cancer. In the absence of contraindications, premenopausal women undergoing RRSO should be offered hormone therapy until menopause. Systemic hormone replacement therapy, is not recommended for women who have had a personal history of breast cancer. RRSO should be considered for breast cancer risk reduction in women younger than 50 years. After a breast cancer diagnosis, RRSO for breast cancer mortality reduction can be considered within two years to women who harbour a pathogenic or likely pathogenic variant in BRCA1 if younger than the recommended age range for ovarian cancer risk reduction. RRSO before the age of 40 and specifically for breast cancer treatment in BRCA2 should be considered only if recommended by their breast cancer oncologist. Following RRSO, it is not recommended to do surveillance for peritoneal cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"39"},"PeriodicalIF":1.7,"publicationDate":"2021-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39450723","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":"Improving our model of cascade testing for hereditary cancer risk by leveraging patient peer support: a concept report.","authors":"Suzanne C O'Neill, Jada G Hamilton, Claire C Conley, Beth N Peshkin, Rosalba Sacca, Glynnis A McDonnell, Claudine Isaacs, Mark E Robson, Kenneth P Tercyak","doi":"10.1186/s13053-021-00198-7","DOIUrl":"10.1186/s13053-021-00198-7","url":null,"abstract":"<p><p>Consensus and evidence suggest that cascade testing is critical to achieve the promise of cancer genetic testing. However, barriers to cascade testing include effective family communication of genetic risk information and family members' ability to cope with genetic risk. These barriers are further complicated by the developmental needs of unaffected family members during critical windows for family communication and adaptation. Peer support could address these barriers. We provide two illustrative examples of ongoing BRCA1/2-related clinical trials that apply a peer support model to improve family communication and functioning. Peer support can augment currently available genetic services to facilitate adjustment to and effective use of cancer genetic risk information. Importantly, this scalable approach can address the presence of cancer risk within families across multiple developmental stages. This applies a family-centered perspective that accommodates all potentially at-risk relatives. This peer support model can be further applied to emerging topics in clinical genetics to expand reach and impact.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"40"},"PeriodicalIF":1.7,"publicationDate":"2021-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39449629","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":"Descriptive study on subjective experience of genetic testing with respect to relationship, family planning and psychosocial wellbeing among women with lynch syndrome.","authors":"Mari Kalamo,&nbsp;Johanna Mäenpää,&nbsp;Toni Seppälä,&nbsp;Jukka-Pekka Mecklin,&nbsp;Kirsi Pylvänäinen,&nbsp;Synnöve Staff","doi":"10.1186/s13053-021-00194-x","DOIUrl":"https://doi.org/10.1186/s13053-021-00194-x","url":null,"abstract":"<p><strong>Background: </strong>Due to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown.</p><p><strong>Methods: </strong>Seventy-nine carriers of germline MMR gene pathogenic variant (path_MMR) were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not having undergone hysterectomy or oophorectomy. These women were sent a questionnaire concerning family planning, intimate relationships and psychosocial wellbeing.</p><p><strong>Results: </strong>Thirty-five women (44.3%) responded. Parity of path_MMR carriers (2.1) was slightly higher than parity among Finnish women in general (1.8). No significant differences were found between parity, number of induced abortions or sterilizations before and after genetic testing. Only minority of subjects reported any influence on family planning (20%) or negative impact on feminine self and body image (14%).</p><p><strong>Conclusions: </strong>The positive germline testing does not seem to have a major negative impact on family planning, intimate relationships or feminine self and body image. According to the open comments, counselling, supportive and empathic attitude of the professionals seem to have a significant impact on this. These results are a valuable addition to the counselling of LS women at reproductive age.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"38"},"PeriodicalIF":1.7,"publicationDate":"2021-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39417065","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":"Correction to: Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants.","authors":"Krithika Murali,&nbsp;Tanya M Dwarte,&nbsp;Mehrdad Nikfarjam,&nbsp;Katherine M Tucker,&nbsp;Rhys B Vaughan,&nbsp;Marios Efthymiou,&nbsp;Allison Collins,&nbsp;Allan D Spigelman,&nbsp;Lucinda Salmon,&nbsp;Amber L Johns,&nbsp;David B Williams,&nbsp;Martin B Delatycki,&nbsp;Thomas John,&nbsp;Alina Stoita","doi":"10.1186/s13053-021-00195-w","DOIUrl":"https://doi.org/10.1186/s13053-021-00195-w","url":null,"abstract":"","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"37"},"PeriodicalIF":1.7,"publicationDate":"2021-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39414270","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":"Population or family history based BRCA gene tests of breast cancer? A systematic review of economic evaluations.","authors":"Zahra Meshkani,&nbsp;Ali Aboutorabi,&nbsp;Najmeh Moradi,&nbsp;Mostafa Langarizadeh,&nbsp;Ali Ghanbari Motlagh","doi":"10.1186/s13053-021-00191-0","DOIUrl":"10.1186/s13053-021-00191-0","url":null,"abstract":"<p><strong>Background: </strong>Nearly 56% of at-risk carriers are not identified and missed as a result of the current family-history (FH) screening for genetic testing. The present study aims to review the economic evaluation studies on BRCA genetic testing strategies for screening and early detection of breast cancer.</p><p><strong>Methods: </strong>This systematic literature review is conducted within the Cochrane Library, PubMed, Scopus, Web of Science, ProQuest, and EMBASE databases. In this paper, the relevant published economic evaluation studies are identified by following the standard Cochrane Collaboration methods and adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement reporting some recommendations for articles up to March 2020. Thereafter, the inclusion and exclusion criteria are applied to screen the articles. Disagreements are resolved through a consensus meeting. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist is used in the evaluation of quality. Finally, a narrative synthesis is performed. To compare the different levels of incremental cost-effectiveness ratio (ICER), the net present value is calculated based on a discount rate of 3% in 2019.</p><p><strong>Results: </strong>Among 788 initially retrieved citations, 12 studies were included. More than 60% of the studies were originated from high-income countries and were published after 2016. It is noteworthy that most of the studies evaluated the payer perspective. Moreover, the robustness of the results were analyzed through one-way and probabilistic sensitivity analyses in nearly 66% of these studies. Nearly, 25% of the studies are focused and defined population-based and family history BRCA tests as comparators; afterwards, the cost-effectiveness of the former was confirmed. The highest and lowest absolute values for the ICERs were $65,661 and $9 per quality adjusted life years, respectively. All studies met over 70% of the CHEERs criteria checklist, which was considered as 93% of high quality on average as well.</p><p><strong>Conclusions: </strong>The genetic BRCA tests for the general population as well as unselected breast cancer patients were cost-effective in high and upper-middle income countries and those with prevalence of gene mutation while population-based genetic tests for low-middle income countries are depended on the price of the tests.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"35"},"PeriodicalIF":1.7,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39361987","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":"Cytotoxic and targeted therapy for BRCA1/2-driven cancers.","authors":"Evgeny N Imyanitov","doi":"10.1186/s13053-021-00193-y","DOIUrl":"https://doi.org/10.1186/s13053-021-00193-y","url":null,"abstract":"<p><p>Tumors arising in BRCA1/2 germline mutation carriers usually demonstrate somatic loss of the remaining BRCA1/2 allele and increased sensitivity to platinum compounds, anthracyclines, mitomycin C and poly (ADP-ribose) polymerase inhibitors (PARPi). Exposure to conventional platinum-based therapy or PARPi results in the restoration of BRCA1/2 function and development of resistance to systemic therapy, therefore, there is a need for other treatment options. Some studies suggested that the use of specific drug combinations or administration of high-dose chemotherapy may result in pronounced tumor responses. BRCA1/2-driven tumors are characterized by increased immunogenicity; promising efficacy of immune therapy has been demonstrated in a number of preclinical and clinical investigations. There are outstanding issues, which require further consideration. Platinum compounds and PARPi have very similar mode of antitumor action and are likely to render cross-resistance to each other, so their optimal position in cancer treatment schemes may be a subject of additional studies. Sporadic tumors with somatically acquired inactivation of BRCA1/2 or related genes resemble hereditary neoplasms with regard to the spectrum of drug sensitivity; the development of user-friendly BRCAness tests presents a challenge. Many therapeutic decisions are now based on the BRCA1/2 status, so the significant reduction of the turn-around time for predictive laboratory assays is of particular importance.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"36"},"PeriodicalIF":1.7,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39362384","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":"Myxofibrosarcoma harboring an MLH1 pathogenic germline variant associated with Muir-Torre syndrome: a case report.","authors":"Makoto Nakagawa,&nbsp;Eisuke Kobayashi,&nbsp;Masayoshi Yamada,&nbsp;Tomoko Watanabe,&nbsp;Makoto Hirata,&nbsp;Noriko Tanabe,&nbsp;Mineko Ushiama,&nbsp;Hiromi Sakamoto,&nbsp;Chiaki Sato,&nbsp;Taisuke Mori,&nbsp;Akihiko Yoshida,&nbsp;Teruhiko Yoshida,&nbsp;Kokichi Sugano,&nbsp;Akira Kawai","doi":"10.1186/s13053-021-00192-z","DOIUrl":"https://doi.org/10.1186/s13053-021-00192-z","url":null,"abstract":"<p><strong>Background: </strong>Muir-Torre syndrome (MTS), which accounts for a small subset (1-3 %) of Lynch syndrome (LS), is an autosomal dominant genetic disorder characterized by sebaceous gland or keratoacanthoma associated with visceral malignancies. Most families with MTS have pathogenic germline variants (PGV) in MSH2. Sarcomas are not common on the LS tumor spectrum, and sarcomas associated with MTS are extremely rare.</p><p><strong>Case presentation: </strong>Here we report a myxofibrosarcoma of the abdominal wall in a 73-year-old man with a sebaceoma that occurred synchronically, leading to a diagnosis of MTS. The loss of MLH1 and PMS2 protein expression was detected in immunohistochemistry, and high-frequency microsatellite instability (MSI-H) was also confirmed. A germline genetic analysis revealed that he harbored the MLH1 PGV.</p><p><strong>Conclusions: </strong>This is the first case of MSI-H myxofibrosarcoma with MTS in an MLH1 PGV carrier. Although rare, we should recognize that sarcomas can be part of the spectrum of LS and MTS.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"34"},"PeriodicalIF":1.7,"publicationDate":"2021-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39332205","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":"Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants.","authors":"Krithika Murali,&nbsp;Tanya M Dwarte,&nbsp;Mehrdad Nikfarjam,&nbsp;Katherine M Tucker,&nbsp;Rhys B Vaughan,&nbsp;Marios Efthymiou,&nbsp;Allison Collins,&nbsp;Allan D Spigelman,&nbsp;Lucinda Salmon,&nbsp;Amber L Johns,&nbsp;David B Williams,&nbsp;Martin B Delatycki,&nbsp;Thomas John,&nbsp;Alina Stoita","doi":"10.1186/s13053-021-00190-1","DOIUrl":"10.1186/s13053-021-00190-1","url":null,"abstract":"<p><strong>Background: </strong>The Australian Pancreatic Cancer Screening Program (APCSP) offers endoscopic ultrasound surveillance for individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) with all participants requiring assessment by a Familial Cancer Service before or after study enrolment.</p><p><strong>Methods: </strong>Individuals aged 40-80 years (or 10 years younger than the earliest PDAC diagnosis) were eligible for APCSP study entry if they had 1) ≥ two blood relatives with PDAC (at least one of first-degree association); 2) a clinical or genetic diagnosis of Hereditary Pancreatitis or Peutz-Jeghers syndrome irrespective of PDAC family history; or 3) a known PDAC predisposition germline pathogenic variant (BRCA2, PALB2, CDKN2A, or Lynch syndrome) with ≥one PDAC-affected first- or second-degree relative. Retrospective medical record review was conducted for APCSP participants enrolled at the participating Australian hospitals from January 2011 to December 2019. We audited the genetic investigations offered by multiple Familial Cancer Services who assessed APCSP participants according to national guidelines, local clinical protocol and/or the availability of external research-funded testing, and the subsequent findings. Descriptive statistical analysis was performed using Microsoft Excel.</p><p><strong>Results: </strong>Of 189 kindreds (285 participants), 50 kindreds (71 participants) had a known germline pathogenic variant at enrolment (BRCA2 n = 35, PALB2 n = 6, CDKN2A n = 3, STK11 n = 3, PRSS1 n = 2, MLH1 n = 1). Forty-eight of 136 (35%) kindreds with no known germline pathogenic variant were offered mutation analysis; 89% was clinic-funded, with increasing self-funded testing since 2016. The relatively low rates of genetic testing performed reflects initial strict criteria for clinic-funded genetic testing. New germline pathogenic variants were detected in five kindreds (10.4%) after study enrolment (BRCA2 n = 3 kindreds, PALB2 n = 1, CDKN2A n = 1). Of note, only eight kindreds were reassessed by a Familial Cancer Service since enrolment, with a further 21 kindreds identified as being suitable for reassessment.</p><p><strong>Conclusion: </strong>Germline pathogenic variants associated with PDAC were seen in 29.1% of our high-risk cohort (55/189 kindreds; 82/285 participants). Importantly, 10.4% of kindreds offered genetic testing were newly identified as having germline pathogenic variants, with majority being BRCA2. As genetic testing standards evolve rapidly in PDAC, 5-yearly reassessment of high-risk individuals by Familial Cancer Services is warranted.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"19 1","pages":"33"},"PeriodicalIF":1.7,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39329156","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}