Hereditary Cancer in Clinical Practice最新文献

{"title":"The Prospective Lynch Syndrome Database: background, design, main results and complete MySQL code.","authors":"Pål Møller","doi":"10.1186/s13053-022-00243-z","DOIUrl":"https://doi.org/10.1186/s13053-022-00243-z","url":null,"abstract":"<p><p>A brief description of why and for which purposes the Prospective Lynch Syndrome Database was established, the principles and design, and the main classes of results are given. Data input is assumption-free input enabling validation of paradigms used to explain the results. The design is considering cancer/age as discrete events to occur or not in a time dimension in a closed room compliant with population genetic paradigms and last centuries developing paradigms of interpreting discrete events reflecting conditional and/or co-occurring stochastic probabilities. Which may be in contrast to the paradigm that any observed event has a cause. The results may indicate that some current paradigms on carcinogenesis should be reconsidered. The complete analytic code in MySQL© syntax together with a flowchart illustrating how the different pieces of codes interrelate are included as supplementary files, enabling third parties to use or modify the code to examine prospectively observed events in their own activities when referring to this report as the source.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10327892","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":"Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium.","authors":"Pål Møller, Toni Seppälä, James G Dowty, Saskia Haupt, Mev Dominguez-Valentin, Lone Sunde, Inge Bernstein, Christoph Engel, Stefan Aretz, Maartje Nielsen, Gabriel Capella, Dafydd Gareth Evans, John Burn, Elke Holinski-Feder, Lucio Bertario, Bernardo Bonanni, Annika Lindblom, Zohar Levi, Finlay Macrae, Ingrid Winship, John-Paul Plazzer, Rolf Sijmons, Luigi Laghi, Adriana Della Valle, Karl Heinimann, Elizabeth Half, Francisco Lopez-Koestner, Karin Alvarez-Valenzuela, Rodney J Scott, Lior Katz, Ido Laish, Elez Vainer, Carlos Alberto Vaccaro, Dirce Maria Carraro, Nathan Gluck, Naim Abu-Freha, Aine Stakelum, Rory Kennelly, Des Winter, Benedito Mauro Rossi, Marc Greenblatt, Mabel Bohorquez, Harsh Sheth, Maria Grazia Tibiletti, Leonardo S Lino-Silva, Karoline Horisberger, Carmen Portenkirchner, Ivana Nascimento, Norma Teresa Rossi, Leandro Apolinário da Silva, Huw Thomas, Attila Zaránd, Jukka-Pekka Mecklin, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepisto, Päivi Peltomäki, Christina Therkildsen, Lars Joachim Lindberg, Ole Thorlacius-Ussing, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Robert Hüneburg, Aída Falcón de Vargas, Andrew Latchford, Anne-Marie Gerdes, Ann-Sofie Backman, Carmen Guillén-Ponce, Carrie Snyder, Charlotte K Lautrup, David Amor, Edenir Palmero, Elena Stoffel, Floor Duijkers, Michael J Hall, Heather Hampel, Heinric Williams, Henrik Okkels, Jan Lubiński, Jeanette Reece, Joanne Ngeow, Jose G Guillem, Julie Arnold, Karin Wadt, Kevin Monahan, Leigha Senter, Lene J Rasmussen, Liselotte P van Hest, Luigi Ricciardiello, Maija R J Kohonen-Corish, Marjolijn J L Ligtenberg, Melissa Southey, Melyssa Aronson, Mohd N Zahary, N Jewel Samadder, Nicola Poplawski, Nicoline Hoogerbrugge, Patrick J Morrison, Paul James, Grant Lee, Rakefet Chen-Shtoyerman, Ravindran Ankathil, Rish Pai, Robyn Ward, Susan Parry, Tadeusz Dębniak, Thomas John, Thomas van Overeem Hansen, Trinidad Caldés, Tatsuro Yamaguchi, Verónica Barca-Tierno, Pilar Garre, Giulia Martina Cavestro, Jürgen Weitz, Silke Redler, Reinhard Büttner, Vincent Heuveline, John L Hopper, Aung Ko Win, Noralane Lindor, Steven Gallinger, Loïc Le Marchand, Polly A Newcomb, Jane Figueiredo, Daniel D Buchanan, Stephen N Thibodeau, Sanne W Ten Broeke, Eivind Hovig, Sigve Nakken, Marta Pineda, Nuria Dueñas, Joan Brunet, Kate Green, Fiona Lalloo, Katie Newton, Emma J Crosbie, Miriam Mints, Douglas Tjandra, Florencia Neffa, Patricia Esperon, Revital Kariv, Guy Rosner, Walter Hernán Pavicic, Pablo Kalfayan, Giovana Tardin Torrezan, Thiago Bassaneze, Claudia Martin, Gabriela Moslein, Aysel Ahadova, Matthias Kloor, Julian R Sampson, Mark A Jenkins","doi":"10.1186/s13053-022-00241-1","DOIUrl":"10.1186/s13053-022-00241-1","url":null,"abstract":"<p><strong>Objective: </strong>To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants.</p><p><strong>Methods: </strong>CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands.</p><p><strong>Results: </strong>In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups.</p><p><strong>Conclusions: </strong>Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9918770","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":"Modifier genes and Lynch syndrome: some considerations.","authors":"Rodney J Scott","doi":"10.1186/s13053-022-00240-2","DOIUrl":"https://doi.org/10.1186/s13053-022-00240-2","url":null,"abstract":"<p><p>Lynch Syndrome (LS) is a highly variable entity with some patients presenting at very young ages with malignancy whereas others may never develop a malignancy yet carry an unequivocal genetic predisposition to disease. The most frequent LS malignancy remains colorectal cancer, a disease that is thought to involve genetic as well as environmental factors in its aetiology. Environmental insults are undeniably associated with cancer risk, especially those imparted by such activities as smoking and excessive alcohol consumption. Notwithstanding, in an inherited predisposition the expected exposures to an environmental insult are considered to be complex and require knowledge about the respective exposure and how it might interact with a genetic predisposition. Typically, smoking is one of the major confounders when considering environmental factors that can influence disease expression on a background of significant genetic risk. In addition to environmental triggers, the risk of developing a malignancy for people carrying an inherited predisposition to disease can be influenced by additional genetic factors that do not necessarily segregate with a disease predisposition allele. The purpose of this review is to examine the current state of modifier gene detection in people with a genetic predisposition to develop LS and present some data that supports the notion that modifier genes are gene specific thus explaining why some modifier gene studies have failed to identify associations when this is not taken into account.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33458650","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":"Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis.","authors":"Olga Caramelo, Cristina Silva, Francisco Caramelo, Cristina Frutuoso, Leonor Pinto, Teresa Almeida-Santos","doi":"10.1186/s13053-022-00242-0","DOIUrl":"10.1186/s13053-022-00242-0","url":null,"abstract":"<p><strong>Purpose: </strong>Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy.</p><p><strong>Methods: </strong>PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC.</p><p><strong>Results: </strong>Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary.</p><p><strong>Conclusions: </strong>Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33455828","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":"Mainstream genetic testing for women with ovarian cancer provides a solid basis for patients to make a well-informed decision about genetic testing.","authors":"Kyra Bokkers,&nbsp;Eveline M A Bleiker,&nbsp;Jacob P Hoogendam,&nbsp;Mary E Velthuizen,&nbsp;Henk W R Schreuder,&nbsp;Cornelis G Gerestein,&nbsp;Joost G Lange,&nbsp;Jacqueline A Louwers,&nbsp;Marco J Koudijs,&nbsp;Margreet G E M Ausems,&nbsp;Ronald P Zweemer","doi":"10.1186/s13053-022-00238-w","DOIUrl":"https://doi.org/10.1186/s13053-022-00238-w","url":null,"abstract":"<p><strong>Background: </strong>There is a growing need for genetic testing of women with epithelial ovarian cancer. Mainstream genetic testing provides an alternative care pathway in which non-genetic healthcare professionals offer pre-test counseling themselves. We aimed to explore the impact of mainstream genetic testing on patients' experiences, turnaround times and adherence of non-genetic healthcare professionals to the mainstream genetic testing protocol.</p><p><strong>Methods: </strong>Patients receiving pre-test counseling at the gynecology departments between April 2018 and April 2020 were eligible to participate in our intervention group. Patients receiving pre-test counseling at the genetics department between January 2017 and April 2020 were eligible to participate in our control group. We evaluated patients' experiences with questionnaires, consisting of questions regarding knowledge, satisfaction and psychosocial outcomes. Patients in the intervention group were sent two questionnaires: one after pre-test counseling and one after receiving their DNA test result. Patients in our control group were sent one questionnaire after receiving their test result. In addition, we collected data regarding turnaround times and adherence of non-genetic healthcare professionals to the mainstream genetic testing protocol.</p><p><strong>Results: </strong>Participation was 79% in our intervention group (105 out of 133 patients) and 60% in our control group (91 out of 152 patients). Knowledge regarding genetics, decisional conflict, depression, anxiety, and distress were comparable in the two groups. In the intervention group, the risk of breast cancer in patients carrying a pathogenic germline variant was discussed less often (49% versus 74% in control group, p ≤ 0.05), and the mean score of regret about the decision to have genetic testing was higher than in the control group (mean 12.9 in the intervention group versus 9.7 in the control group, p ≤ 0.05), although below the clinically relevant threshold of 25. A consent form for the DNA test and a checklist to assess family history were present for ≥ 95% of patients in the intervention group.</p><p><strong>Conclusion: </strong>Mainstream genetic testing is an acceptable approach to meet the increase in genetic testing among women with epithelial ovarian cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33450929","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":"Low-level constitutional mosaicism of BRCA1 in two women with young onset ovarian cancer.","authors":"B Speight,&nbsp;E Colvin,&nbsp;E D Epurescu,&nbsp;J Drummond,&nbsp;S Verhoef,&nbsp;M Pereira,&nbsp;D G Evans,&nbsp;M Tischkowitz","doi":"10.1186/s13053-022-00237-x","DOIUrl":"https://doi.org/10.1186/s13053-022-00237-x","url":null,"abstract":"<p><p>Germline pathogenic variants in BRCA1 and BRCA2 cause hereditary breast and ovarian cancer. The vast majority of these variants are inherited from a parent. De novo constitutional pathogenic variants are rare. Even fewer cases of constitutional mosaicism have been reported and these have mostly been described in women with breast cancer. Here we report low-level constitutional mosaicism identified by Next Generation Sequencing in two women with ovarian cancer. A BRCA1 c.5074G > A p.(Asp1692Asn) variant detected in the first female at 42 years, classed as likely pathogenic, was found in ~ 52% of reads in DNA extracted from tumour, ~ 10% of reads in DNA extracted from peripheral blood leukocytes and ~ 10% of reads in DNA extracted from buccal mucosa. The second BRCA1 c.2755_2758dupCCTG p.(Val920AlafsTer6) variant was detected in a female aged 53 years, classed as pathogenic, and was found in ~ 59% of reads in DNA extracted from tumour, ~ 14% of reads in DNA extracted from peripheral blood leukocytes and similarly in ~ 14% of reads in both DNA extracted from buccal mucosa and urine sample. Sanger sequencing confirmed the presence of these variants at a corresponding low level consistent with mosaicism that may not have been detected by this method alone. This report demonstrates the clinical benefit for two women of BRCA1/BRCA2 germline NGS testing at a depth that can detect low-level mosaicism. As well as informing appropriate treatments, tumour sequencing results may facilitate the detection and interpretation of low-level mosaic variants in the germline. Both results have implications for other cancer risks and for relatives when providing a family cancer risk assessment and reproductive risk. The implications for laboratory practice, clinical genetics management and genetic counselling for constitutional mosaicism of BRCA1/BRCA2 are discussed.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40354805","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":"Attitudes toward preimplantation genetic testing and quality of life among individuals with hereditary diffuse gastric cancer syndrome.","authors":"Ibrahim H Shah, Erin E Salo-Mullen, Kimberly A Amoroso, David Kelsen, Zsofia K Stadler, Jada G Hamilton","doi":"10.1186/s13053-022-00239-9","DOIUrl":"10.1186/s13053-022-00239-9","url":null,"abstract":"<p><strong>Background: </strong>Hereditary Diffuse Gastric Cancer (HDGC) syndrome is an autosomal dominant hereditary cancer predisposition associated with germline pathogenic/likely pathogenic variants in the CDH1 gene. Identifying early stage HDGC is difficult, and prophylactic measures can be effective in preventing incidence. Preimplantation Genetic Testing (PGT) can provide information about CDH1 variant status, HDGC risk, and limit familial transmission of CDH1 variants. To date, however, little is known about the attitudes of individuals with CDH1 variants towards PGT.</p><p><strong>Methods: </strong>Given that little is known about the reproductive attitudes of individuals with HDGC, we recruited participants with CDH1 variants from a familial gastric cancer registry and administered a cross-sectional survey with open- and closed-ended response items. We assessed attitudes regarding PGT and the effect of HDGC on quality of life.</p><p><strong>Results: </strong>Participants (n = 21) were predominantly partnered (61.9%), had a personal cancer history (71.4%), and had biological children (71.4%). Interest in learning about PGT was high; 66.7% of participants were interested in PGT and 90.5% approved of healthcare providers discussing PGT with individuals with CDH1 variants. Attitudes regarding personal use were varied. Among all participants, 35% would not, 25% were uncertain, and 40% would use PGT. Personal philosophy and preferences for family and reproduction were key factors related to PGT attitudes. HDGC had moderate effects on participants' quality of life, including social relationships, health behaviors, and emotional experiences including worry about cancer risk and guilt regarding familial implications.</p><p><strong>Conclusion: </strong>PGT was identified by participants as acceptable for use in a variety of contexts and benefits of reproductive counseling involving PGT may extend beyond CDH1 carriers to family members' reproductive behaviors. Dispositions towards PGT are governed by personal philosophy or belief systems. These findings can help guide providers counseling individuals with CDH1 variants.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40346045","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":"Barriers and facilitators to using aspirin for preventive therapy: a qualitative study exploring the views and experiences of people with Lynch syndrome and healthcare providers.","authors":"Kelly E Lloyd, Robbie Foy, Louise H Hall, Lucy Ziegler, Sophie M C Green, Zainab F Haider, David G Taylor, Mairead MacKenzie, Samuel G Smith","doi":"10.1186/s13053-022-00235-z","DOIUrl":"10.1186/s13053-022-00235-z","url":null,"abstract":"<p><strong>Background: </strong>The National Institute for Health and Care Excellence (NG151) recommends considering daily aspirin for people with Lynch syndrome to reduce colorectal cancer risk. However, deciding whether to initiate aspirin could be a complex decision for patients and their healthcare providers, as both the potential benefits and harms need to be considered.</p><p><strong>Methods: </strong>We conducted semi-structured interviews to explore the barriers and facilitators to using aspirin for preventive therapy. We recruited 15 people with Lynch syndrome, and 23 healthcare providers across multiple professions in primary, and specialist care (e.g. clinical genetics) in the United Kingdom. Interview schedules were informed by the Theoretical Domains Framework.</p><p><strong>Results: </strong>There were three themes: 1) Considering potential harms and benefits; 2) Healthcare pathway; 3) Patients' level of interest in aspirin. All healthcare providers, across primary and specialist care, viewed general practitioners (GPs) as being responsible for prescribing and overseeing the use of aspirin. However, GPs were unfamiliar with aspirin for preventive therapy, and concerned about prescribing at higher doses (300-600 mg). To support decision-making, GPs wanted clarification from specialist clinicians on the evidence and dose to prescribe. Not all participants with Lynch syndrome received information on aspirin from their healthcare provider, and several were unsure who to discuss aspirin with. GPs were more inclined to prescribe aspirin for patients with expressed preferences for the medication, however several patients were uncertain and wanted further guidance.</p><p><strong>Conclusions: </strong>Coordinated and multilevel strategies are needed, addressing the needs of both GPs and people with Lynch syndrome, to ensure consistent implementation of national guidance on aspirin for preventive therapy.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40720993","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":"BRCA1/2 variants and copy number alterations status in non familial triple negative breast cancer and high grade serous ovarian cancer.","authors":"Fatima Zahra El Ansari,&nbsp;Farah Jouali,&nbsp;Rim Fekkak,&nbsp;Joaira Bakkach,&nbsp;Naima Ghailani Nourouti,&nbsp;Amina Barakat,&nbsp;Mohcine Bennani Mechita,&nbsp;Jamal Fekkak","doi":"10.1186/s13053-022-00236-y","DOIUrl":"https://doi.org/10.1186/s13053-022-00236-y","url":null,"abstract":"<p><strong>Background: </strong>While the role of BRCA1/2 genes in familial breast and ovarian cancer is well established, their implication in the sporadic form of both cancers is still controversial. With the development of poly (ADP-ribose) polymerase (PARP) inhibitors, the exact relationship between BRCA1/2 genes and sporadic triple negative breast cancer/high grade serous carcinoma (TNBC/HGSC) needs to be further investigated. Therefore, we conducted a study in which we analyze BRCA1/2 point mutations and copy number alterations in Moroccan patients suffering from TNBC/HGSC.</p><p><strong>Methods: </strong>To achieve our goal, we analyzed BRCA1/2 genes in the FFPE tissue blocks and blood samples of 65 TNBC/HGSC selected patients, using next generation sequencing technology.</p><p><strong>Results: </strong>From the 65 successfully sequenced patients in our cohort, we detected five-point variants in six different patients, four variants were classified as pathogenic and one of unknown significance. Regarding copy number alterations we detected one copy number loss in BRCA1 gene and one copy number gain in BRCA2 gene. The genetic screening of BRCA1/2 genes using these patients' genomic DNA indicated that five harbored a germline genetic alteration. While three harbored a somatic genetic alteration. To the best of our knowledge, three-point variants detected in our study have never been reported before.</p><p><strong>Conclusion: </strong>According to the results found in the present study, in a population without a family history of cancer, the possibility of a BRCA1/2 somatic pathogenic variant in high grade serous carcinoma is 7%. While for Triple negative breast cancer somatic point variants and copy number alterations seems to be a very rare genetic event.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40709704","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":"Unravelling genetic variants of a swedish family with high risk of prostate cancer.","authors":"Serena Barilla, Annika Lindblom, Hafdis T Helgadottir","doi":"10.1186/s13053-022-00234-0","DOIUrl":"10.1186/s13053-022-00234-0","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer is the most prevalent cancer in men worldwide. It is a polygenic disease with a substantial proportion of heritability. Identification of novel candidate biomarkers is crucial for clinical cancer prevention and the development of therapeutic strategies. Here, we describe the analysis of rare and common genetic variants that can predispose to the development of prostate cancer.</p><p><strong>Methods: </strong>Whole-genome sequencing was performed on germline DNA of five Swedish siblings which were diagnosed with prostate cancer. The high-risk variants were identified setting the minor allele frequency < 0.01, CADD > 10 and if tested in PRACTICAL, OR > 1.5, while the low-risk variants were identified minor allele frequency > 0.01, CADD > 10 and if tested in PRACTICAL, OR > 1.1.</p><p><strong>Results: </strong>We identified 38 candidate high-risk gene variants and 332 candidate low-risk gene variants, where 2 and 14 variants were in coding regions, respectively, that were shared by the brothers with prostate cancer.</p><p><strong>Conclusions: </strong>This study expanded the knowledge of potential risk factor candidates involved in hereditary and familial prostate cancer. Our findings can be beneficial when applying targeted screening in families with a high risk of developing the disease.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2022-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40532968","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}