Hereditary Cancer in Clinical Practice最新文献

{"title":"Association analysis of germline mutations in CHEK2, PALB2, NBN and RECQL with the risk of ductal carcinoma in situ in Polish women.","authors":"Sylwia Feszak, Wojciech Kluźniak, Igor Feszak, Magdalena Chady, Dominika Wokołorczyk, Klaudia Stempa, Helena Rudnicka, Katarzyna Gliniewicz, Anna Jakubowska, Marcin Lener, Maciej Czepukowicz, Tomasz Huzarski, Tadeusz Dębniak, Jacek Gronwald, Jan Lubiński, Cezary Cybulski","doi":"10.1186/s13053-025-00320-z","DOIUrl":"10.1186/s13053-025-00320-z","url":null,"abstract":"<p><p>BACKGROUND: The genetic background of ductal carcinoma in situ (DCIS) has not been well explored. Previously, we reported that Polish founder mutations of BRCA1/2 confer susceptibility to DCIS. The aim of our study was to investigate the role of CHEK2, PALB2, NBN and RECQL mutations in the ethology of DCIS. METHODS: We studied 564 Polish women with DCIS for eight Polish founder alleles, including four in CHEK2 (c.1100delC, c.444 + 1G > A, del5395 and c.470T > C), two in PALB2 (c.509_510delGA and c.172_175delTTGT), one in NBN (c.657_661delACAAA) and one in RECQL (c.1667_1667 + 3delAGTA). To investigate the association of these alleles with DCIS risk, we used mutation frequencies in cancer-free controls as a reference (4000 to 4702 controls for different variants). To analyze survival, patients were followed on average for 156 months. RESULTS: A CHEK2 mutation (all variants combined) was associated with an increased risk of DCIS (OR = 1.7, p = 0.003). The risk was higher for CHEK2 truncating mutations (OR = 3.0, p = 0.001) than for a missense variant c.470T > C (OR = 1.5, p = 0.04). The risk was highest for carriers of CHEK2 truncating mutations with a family history of breast cancer (OR = 4.2, p = 0.01). There were no deaths reported in 52 CHEK2 mutation carriers during the follow up time. PALB2, NBN and RECQL mutations were rare among cases and were not associated with DCIS risk in Polish women. CONCLUSIONS: Based on the current study, women with a CHEK2 mutation face an increased risk of DCIS. The presence of DCIS should be considered during surveillance of CHEK2 mutation carriers. On the other hand, DCIS patients should receive genetic counseling and testing for CHEK2 mutations. </p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"19"},"PeriodicalIF":2.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796170","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 promoter hypermethylation is not associated with germline variants in Polish breast cancer patients.","authors":"Karolina Prajzendanc, Paweł Domagała, Jolanta Hybiak, Wojciech Kluźniak, Cezary Cybulski, Katarzyna Białkowska, Alicja Ogrodniczak, Janusz Ryś, Aleksandra Sejda, Marek Szwiec, Joanna Tomiczek-Szwiec, Tomasz Kluz, Roksana Dwornik, Dagmara Cylwik, Jacek Gronwald, Jan Lubiński, Anna Jakubowska","doi":"10.1186/s13053-025-00317-8","DOIUrl":"10.1186/s13053-025-00317-8","url":null,"abstract":"<p><p>BACKGROUND: Methylation of BRCA1 has been associated with an increased risk of breast cancer and specific clinical characteristics of the disease. In the British population, the genetic alteration c.-107 A/T has been shown to cause allelic methylation, leading to familial breast and ovarian cancer. However, this variant has not been detected in Polish population. Nonetheless, other genetic variants may still be associated with BRCA1 methylation, highlighting the need for further research. AIM OF STUDY: This study aimed to analyze BRCA1 promoter region to identify germline alterations associated with BRCA1 methylation in peripheral blood DNA. Additionally, the correlation between the detected variants and breast cancer incidence, as well as clinical characteristics, was assessed. MATERIALS AND METHODS: One hundred breast cancer patients with BRCA1 methylation were analyzed using pyrosequencing to quantify methylation levels. Immunohistochemistry (IHC) was performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from these patients to assess BRCA1 expression. In 47 patients with the highest BRCA1 methylation and decreased BRCA1 expression, Sanger sequencing was performed encompassing 643 bp of BRCA1 promoter to identify potential variants associated with methylation and/or breast cancer. A variant was identified and genotyped in multiple patient groups, including 336 BRCA1 methylation-positive women, 1898 unselected breast cancer cases, 2234 healthy controls, and 309 BRCA1 pathogenic variant (PV) carriers. Statistical analyses were performed using Fisher’s exact test and Chi-square test in Stata/IC version 16.1. RESULTS: The study identified BRCA1 c.20 + 101 C/G (rs799905) in the promoter region of the gene. However, no significant association was found between rs799905 and BRCA1 methylation or breast cancer risk. Nevertheless, a borderline association was observed between rs799905 and the occurrence of triple-negative breast cancer (TNBC) (p = 0.048) as well as lymph node (LN) metastases (p = 0.046). Among BRCA1 PV carriers, the GG genotype was significantly more frequent, while the CC genotype was 10 times less common compared to non-carriers (p = 0.003). CONCLUSION: Rs799905 variant is not associated with BRCA1 methylation breast cancer risk. However, it may be linked to the occurrence of TNBC and LN metastases. Additionally, rs799905 may be associated to some extent with BRCA1 PVs, though further research is needed to clarify the nature of this potential correlation. </p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"18"},"PeriodicalIF":2.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267913","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":"Translation, cultural adaptation, and pilot testing of the German cancer worry scale among BRCA1/2 pathogenic variant carriers in Austria.","authors":"Anna-Maria Parger, Daniela Muhr, Christian F Singer, Yen Y Tan","doi":"10.1186/s13053-025-00316-9","DOIUrl":"10.1186/s13053-025-00316-9","url":null,"abstract":"<p><strong>Background: </strong>Cancer-related worry can significantly impact psychosocial wellbeing and decision-making, especially among individuals with hereditary cancer risk. Although the Cancer Worry Scale is a commonly used instrument, no culturally adapted version exists for German speaking populations. This study aimed to translate, culturally adapt and pilot-test a German version of the 8-item Cancer Worry Scale in individuals carrying BRCA1 or BRCA2 pathogenic variants in Austria.</p><p><strong>Methods: </strong>The scale was translated using a forward and backward translation process, and reviewed by an expert panel. Participants were recruited from a familial cancer clinic and completed the translated scale along with demographic questions. Participants provided feedback on item clarity and comprehension, which informed minor revisions. The final version was then pilot-tested with a small sample of BRCA1/2 carriers.</p><p><strong>Results: </strong>Thirty-five individuals with BRCA1/2 pathogenic variants completed the scale. Most participants found the scale understandable, though eight reported difficulties with certain items. Based on this feedback, four items were revised to improve clarity. Descriptive analysis indicated similar worry patterns to those observed in international studies. Women who had not undergone risk-reducing surgery reported higher cancer worry, while male participants expressed elevated concern primarily for the health of their family members.</p><p><strong>Conclusion: </strong>This pilot study presents the first pilot-tested German version of the 8-item Cancer Worry Scale. While initial results support its feasibility and comprehension, further research is needed to validate the psychometric properties of the instrument in larger German-speaking populations.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"17"},"PeriodicalIF":2.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102001","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":"Knowledge and perceptions of genetic testing for patients with breast cancer in Nigeria: a survey of healthcare providers.","authors":"Funmilola Olanike Wuraola, Anna Dare, Jenine Ramruthan, Emma Reel, Anna T Santiago, Folorunso Sharif, Agodirin Olayide, Nneka Sunday-Nweke, Olusegun Alatise, Tulin D Cil","doi":"10.1186/s13053-025-00315-w","DOIUrl":"10.1186/s13053-025-00315-w","url":null,"abstract":"<p><strong>Background: </strong>The role of genetics in breast cancer management is becoming increasingly essential in sub-Saharan Africa (SSA). Harmonized Guidelines by the National Comprehensive Cancer Network (NCCN) for SSA outline the subset of patients requiring genetic testing for hereditary breast cancer as part of their treatment plan. However, in low-and middle-income countries (LMICs) like Nigeria, access to genetic counselling and testing remains limited. Additionally, the knowledge and acceptability of these available services from the healthcare provider (HCP) perspective are largely unknown. This study aimed to assess the knowledge and perceptions of hereditary breast cancer testing among HCPs in Nigeria.</p><p><strong>Methods: </strong>In June 2022, we conducted a survey among 549 Nigerian HCPs. The 35-item survey was administered using Google Forms and distributed via WhatsApp. The survey collected demographic data and included three sections on genetic testing in breast cancer patients, focusing on knowledge, perceptions, and training.</p><p><strong>Results: </strong>The results were analyzed using R Version 4.4.1 (R Core Team). Altogether 121 HCPs responded (22% response rate): 54 (44.6%) general surgeons, 4 (3.3%) breast surgical oncologists, 29 (24.0%) clinical and radiation oncologists, 31(25.6%) oncology nurses, and 3 (2.5%) breast radiologists. The survey results indicate that Nigerian HCPs were knowledgeable about hereditary breast cancer genetics, but the implementation of counselling and testing was low. Only 32.2% of respondents had requested genetic testing for their patients, and all testing was done through private laboratories. Only 9.9% had received formal clinical genetics training, and 13.2% reported having a genetic counsellor in their hospital. There was considerable interest in future genetics training programs using in person and online teaching modalities.</p><p><strong>Conclusion: </strong>This survey highlights the need for specialized breast cancer genetic training tailored for Nigerian HCPs, which is essential in achieving breast cancer treatment parity. Addressing the substantial challenges in expanding genetic testing capacity in Nigeria is warranted for future progress.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"16"},"PeriodicalIF":2.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103212","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":"Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants.","authors":"Roksana Dwornik, Katarzyna Białkowska","doi":"10.1186/s13053-025-00313-y","DOIUrl":"https://doi.org/10.1186/s13053-025-00313-y","url":null,"abstract":"<p><p>Pathogenic variants in BRCA1 and BRCA2 are associated with an increased risk of developing several types of cancer, including breast cancer. However, the risk varies by other environmental and genetic factors present in carriers of mutation. To understand the value of these factors more clearly, a number of common genetic susceptibility variants have been studied through genome-wide association studies as potential genetic risk modifiers for BRCA1 and BRCA2 pathogenic variants carriers. Several studies have identified specific polymorphisms that may influence the risk of breast cancer development, either by increasing or reducing susceptibility. These variants are implicated in biological pathways such as DNA damage repair, hormonal regulation or cell proliferation. The identification and understanding of key genetic modifiers may provide valuable insights into development of personalized prevention, targeted therapies and screening strategies for high-risk individuals. This review presents the overview of known genetic risk modifiers for carriers of BRCA1 and BRCA2 pathogenic variants, their potential impact on risk, and their functional roles. Furthermore, it highlights the need for further research directions, including understanding the biological role of genetic modifiers in cancer development and the refinement of risk assessment models.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"15"},"PeriodicalIF":2.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995873","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":"Chemotherapy receipt in affected BRCA1/2 and PALB2 carriers with operable breast cancer: the impact of early detection and pre-diagnostic awareness on clinical outcomes and treatment.","authors":"Stephanie M Wong, Carla Apostolova, Amina Ferroum, Basmah Alhassan, Ipshita Prakash, Mark Basik, Karyne Martel, Sarkis Meterissian, David Fleiszer, Nora Wong, Michaela Bercovitch Sadinsky, Talia Malagon, Jean Francois Boileau, William D Foulkes","doi":"10.1186/s13053-025-00314-x","DOIUrl":"https://doi.org/10.1186/s13053-025-00314-x","url":null,"abstract":"<p><strong>Purpose: </strong>While enhanced breast screening of germline pathogenic variant (GPV) carriers results in earlier stage at diagnosis, the impact of tumour biology and GPV on chemotherapy receipt in early-stage disease remains understudied.</p><p><strong>Methods: </strong>We retrospectively reviewed treatment administered following a first diagnosis of BRCA1/2- and PALB2-associated breast cancer between 2002 and 2022. Chemotherapy receipt was compared according to tumor size, biologic subtype, and GPV. Subgroup analyses were performed in women with T1N0 disease and in those with pre-diagnostic awareness of their GPV.</p><p><strong>Results: </strong>Overall, 309 affected BRCA1/2 and PALB2 carriers with a median age of 43 years at breast cancer diagnosis (range, 19-80 years) were included; 160 (51.8%) BRCA1, 130 (42.1%) BRCA2, and 19 (6.1%) PALB2 carriers. Chemotherapy was administered in 70.9% of index breast cancer cases and was significantly associated with younger age, tumor size, histologic grade, nodal status, and biologic subtype (all p < 0.05). Chemotherapy receipt was 80.6% in BRCA1-associated breast cancers compared to 56.9% in BRCA2 and 84.2% in PALB2 associated breast cancers (p < 0.001). In subgroup analysis of early stage, T1N0 disease, chemotherapy was administered in 78.9% BRCA1 and 59.5% BRCA2/PALB2 patients (p = 0.04). Pre-diagnostic awareness of a GPV in BRCA1/2 or PALB2 was associated with smaller invasive tumors (%T1, 50% vs. 32.9%; p = 0.002) and node-negative invasive disease (87.1% vs. 72.2%), as well as a reduced likelihood of chemotherapy (59.7% vs. 74.3%, p = 0.02).</p><p><strong>Conclusion: </strong>Chemotherapy receipt is high in BRCA1/2 and PALB2-associated breast cancers including in early stage, node-negative disease. Pre-diagnostic awareness is associated with a lower likelihood of requiring chemotherapy for a breast cancer diagnosis.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"14"},"PeriodicalIF":2.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052957","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":"Endoscopic surveillance for colorectal cancer and its precursor lesions in Lynch syndrome; time for some policy shifts?","authors":"Romy N Kuipers, Marissa F Burggraaff, Michiel Hj Maas, Dorien Tj van der Biessen-van Beek, Mariëtte Ca van Kouwen, Tanya M Bisseling","doi":"10.1186/s13053-025-00312-z","DOIUrl":"https://doi.org/10.1186/s13053-025-00312-z","url":null,"abstract":"<p><strong>Background: </strong>While numerous studies have demonstrated variations in colorectal cancer (CRC) incidence among Lynch Syndrome (LS)-associated germline pathogenic variant (gPV) carriers, limited data are available regarding tailoring surveillance and treatment strategies. The main goal of this study was to estimate whether personalised care could be offered based on the different gPVs (MLH1, MSH2, MSH6 or PMS2). Additionally, the outcome from patient-shared care for early (T1) CRC was investigated.</p><p><strong>Methods: </strong>The study is performed as a single centre retrospective analysis of our cohort of patients with a LS-associated gPV in MLH1, MSH2, MSH6 or PMS2. Colon surveillance data from between January 1978 to February 2024 were collected. Analyses were performed to identify differences in incidence of precursor lesions and CRC between the different variants and treatment variation for CRC in LS.</p><p><strong>Results: </strong>From a cohort of 621 LS individuals 496 (133 MLH1, 107 MSH2, 180 MSH6 and 76 PMS2) could be included in this study. Analyses revealed that, despite adequate surveillance intervals and lower adenoma incidence, individuals with a gPV in MLH1 or MSH2 have higher CRC incidences compared to MSH6 or PMS2. Most detected CRC lesions were early stage (T1) CRCs. Treatment for T1 CRC varied considerably; in 68% of the cases deviating from a subtotal colectomy, with nearly equivalent recurrence rates.</p><p><strong>Discussion: </strong>Based on higher precursor lesion detection and lower CRC incidences in LS individuals with a gPV in MSH6 or PMS2 under biannual endoscopic surveillance, this study supports the potential for extended surveillance intervals in the latter group. As treatment for the detected T1 CRCs varied considerably with nearly equivalent recurrence rates, in selected cases less invasive interventions for LS individuals could be considered.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"13"},"PeriodicalIF":2.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065252","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":"Association between single nucleotide polymorphisms of DNA repair genes (BRCA1, BRCA2, and PALB2) and breast cancer incidence in a subset of Iranian population.","authors":"Sepideh Jahangiri, Zahra Abdan, Massoud Houshmand, Ali Souroush, Mozaffar Aznab","doi":"10.1186/s13053-025-00311-0","DOIUrl":"10.1186/s13053-025-00311-0","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the most common malignancy among Iranian females, accounting for 24.4% of all malignancies. Germ line mutations in DNA repair system-related genes are associated with an increased risk of BC. This study aims to evaluate the frequencies of single nucleotide polymorphisms (SNPs) in the BRCA1, BRCA2, and PALB2 genes in patients with BC from a subset of the Iranian population in the western part of Iran.</p><p><strong>Methods: </strong>Blood samples were collected from 335 patients with BC and 354 healthy matched volunteers. Genomic DNA was extracted using the salting-out method and, after quality control, was genotyped using the multiplex TaqMan allelic discrimination assay for three SNPs: rs80359550 (6174 delT) in the BRCA2 gene, rs180177102 in the PALB2 gene, and rs386833395 (185delAG) in the BRCA1 gene. Statistical analysis was performed to examine allele frequency, odds ratio, and relative risk (genetic association) in a retrospective case-control study.</p><p><strong>Results: </strong>The data showed no association between rs386833395 and BC risk in the studied population (odds ratio = 1), whereas rs80359550 and rs180177102 polymorphisms were strongly associated with BC risk in patients (odds ratio = 0.01 for both, with p-values of 0.011 and 0.021, respectively).</p><p><strong>Conclusions: </strong>Our findings suggest no significant association between the rs386833395 polymorphism and BC risk in the Iranian Kurdish population, while rs80359550 and rs180177102 polymorphisms were strongly associated with BC. However, the study has several limitations, including its retrospective design, a relatively small sample size, and the potential lack of generalizability to other ethnic groups within Iran. Future studies involving larger cohorts and more diverse populations are needed to confirm these results.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"12"},"PeriodicalIF":2.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744455","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":"Prostate Cancer: genetics in practice now and in the future.","authors":"Jana McHugh, Elizabeth Bancroft, Zsofia Kote-Jarai, Rosalind Eeles","doi":"10.1186/s13053-025-00310-1","DOIUrl":"10.1186/s13053-025-00310-1","url":null,"abstract":"<p><p>Prostate Cancer (PrCa) is one of the most common cancers worldwide and causes a significant healthcare burden. Recent predictions estimate the incidence of new cases of PrCa will double from 1.4 million in 2020 to 2.9 million by 2040.The known risk factors for PrCa are increasing age, family history, ancestry and genetics. PrCa is one of the most heritable of the more common cancers. The heritability of PrCa is due to both rare moderate to high-risk monogenic variants and more common variants known as single nucleotide polymorphisms (SNPs) which can be used to calculate a polygenic risk score (PRS) for PrCa, while there is some of the genetic risk as yet unexplained. In recent years more PrCa risk-associated SNPs have been identified, increasing over time with the inclusion of more persons of diverse ancestry in studies. The identification of germline variants known to be associated with increased PrCa risk and disease aggressiveness has led to targeted treatments for certain pathogenic variant carriers.This is a mini review of how the genetics of PrCa can impact on screening and early detection of the disease and the treatment and management of the disease when diagnosed.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"11"},"PeriodicalIF":2.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712195","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":"Tumour mutational burden using a targeted panel approach for comprehensive tumour profiling focusing on colorectal cancer.","authors":"Rodney J Scott, Andrew Ziolkowski, David Mossman, Michael Hipwell","doi":"10.1186/s13053-025-00308-9","DOIUrl":"10.1186/s13053-025-00308-9","url":null,"abstract":"<p><p>There is an increasing recognition that comprehensive tumour profiling (CTP) represents an important adjunct to the diagnosis of malignancy providing not only an assessment of how many mutations there are in any given tumour which reflects the probability of immune checkpoint inhibitor success, but also which mutations are associated with targeted therapies, a signature that reflects environmental insult and potentially the identification of cancers of unknown origin.This short review describes an approach to assaying tumour mutational burden (TMB), what the difficulties are in the assessment of the TMB and what it can be applied to in regards to improving patient outcomes. A final section of the review delves into some examples of colorectal cancer studies that identify findings that suggest there remains much to learn about tumour development.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"10"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531431","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}