Hereditary Cancer in Clinical Practice最新文献

{"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}

{"title":"High familial risks in some rare cancers may pinpoint to hidden germline genetics: focus on esophageal, stomach, small intestinal, testis, thyroid and bone cancers.","authors":"Kari Hemminki, Otto Hemminki, Anni Koskinen, Akseli Hemminki, Asta Försti","doi":"10.1186/s13053-024-00303-6","DOIUrl":"10.1186/s13053-024-00303-6","url":null,"abstract":"<p><strong>Background: </strong>Germline genetic susceptibilities of rare cancers of the esophagus, stomach, small intestine, testis, (nonmedullary) thyroid gland and bone with high familial risks are not well known. Here, we use familial risk data from the Swedish Family-Cancer Database which contains records of cancers in Swedish families obtained over a century. We compare familial risks for offspring diagnosed with any of these cancers when their parent had or had not that cancer. We review the global literature of the reported constitutional variants that may explain part of the familial risk.</p><p><strong>Main body: </strong>Familial risks for esophageal and stomach cancers are about 2.0 and apart from early-onset stomach cancer few high-risk variants are known. Genetic studies may be hampered by dominant environmental risk factors for these cancers. Small intestinal carcinoids have a very high familial risk (28 between siblings) but no high-risk genes have been identified to explain this. Low-risk polygenic variants have been identified. Small intestinal adenocarcinoma is a manifestation in Lynch syndrome. Testicular and thyroid cancers are characterized by high familial risk (about 5) which may be explained largely by a polygenic background, although thyroid cancer is a component in a number of rare cancer syndromes. Several predisposing genes have been identified for bone cancer (familial risk 7).</p><p><strong>Conclusions: </strong>The discussed cancers are rare and they present with a relatively high familial risk, in spite of lacking identified high-penetrant constitutional variants. It is possible that the polygenic component, already recognized for testis cancer, is stronger than previously expected. Thus polygenic models with rare high/moderate- and low-risk variants could fit the familial risk and shape the germline genetic landscape of these cancers. Polygenic background may have clinical implications.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"9"},"PeriodicalIF":2.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525271","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":"De novo familial adenomatous polyposis with germline double heterozygosity of APC/BRCA2: a case report and literature review.","authors":"Tian-Qi Zhang, Ji-Dong Cai, Cong Li, Yun Xu, Ye Xu","doi":"10.1186/s13053-025-00306-x","DOIUrl":"10.1186/s13053-025-00306-x","url":null,"abstract":"<p><strong>Background: </strong>The widespread application of colonoscopy screening and genetic testing in colorectal cancer (CRC) treatment has led to the identification of a subset of familial adenomatous polyposis (FAP) patients who lack a family history of the disease but harbor germline gene mutations. Moreover, distinct genotypes may be associated with varied clinical presentations and therapeutic options. This case report describes a male patient with de novo FAP who harbored germline double heterozygosity (GDH) for APC and BRCA2 mutations. The patient underwent total colectomy, and genetic testing enabled personalized surveillance and management strategies for his family members.</p><p><strong>Case presentation: </strong>A 43-year-old male with no family history of cancer presented to the outpatient clinic of the Colorectal Surgery Department with complaints of constipation and hematochezia. Colonoscopy revealed hundreds of polyps throughout the colon and a rectal adenocarcinoma located 5 cm from the anal verge. Gastroduodenal endoscopy did not detect any upper gastrointestinal adenomas. The patient underwent laparoscopic total colectomy with abdominoperineal resection of the rectum and end ileostomy. With the consent of the patient and his family, genetic testing was performed. The index patient was found to carry an APC splicing site mutation (exon 15: c.1744-1G > A) and a BRCA2 missense mutation (exon 17: c.7976G > A: p.R2659K). His daughter was found to have inherited the same germline BRCA2 variant. Additionally, the rectal cancer exhibited proficient DNA mismatch repair (pMMR) status, ERBB2 copy number amplification, and a missense mutation, while the KRAS, NRAS, and BRAF genes were wild-type. Based on the genetic testing results and clinical manifestations, the index patient was diagnosed with familial adenomatous polyposis (FAP) and rectal cancer. Personalized surveillance and management strategies were implemented for the patient and his family, focusing on the risks of extra-colonic diseases and potential malignancies in the prostate, pancreas, breast, and ovaries.</p><p><strong>Conclusion: </strong>De novo FAP with double germline mutations in APC and BRCA2, along with somatic ERBB2 mutations, is exceptionally rare among hereditary cancer cases. With the rapid advancements in genomics, the detection of multiple gene variants in individuals or families has become increasingly common. Additionally, the application of artificial intelligence (AI) in medical research may provide powerful tools for genetic analysis and clinical decision-making. Consequently, a comprehensive evaluation of family history, a deep understanding of hereditary cancer syndromes, and precise interpretation of genetic mutations are essential for personalized clinical management in the era of precision medicine. However, these tasks pose significant challenges for clinicians and genetic counselors alike.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"6"},"PeriodicalIF":2.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473328","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}