Familial Cancer最新文献

{"title":"Genotypic and phenotypic characteristics of germline TP53 variant carriers: experience from two cancer genetic counseling units.","authors":"Beatriz Grau Mirete, Asia Ferrández Arias, Paula Rodríguez Payá, María Valero Revert, David Sánchez Garcia, Mariano Martínez Marín, Javier-David Benítez-Fuentes, Isabel Chirivella González, Ana Beatriz Sánchez Heras","doi":"10.1007/s10689-026-00571-2","DOIUrl":"10.1007/s10689-026-00571-2","url":null,"abstract":"<p><p>Germline TP53 pathogenic or likely pathogenic variants underlie Li-Fraumeni syndrome (LFS), but with broader use of multigene panel (MGP) testing, carriers are increasingly identified outside classic criteria. We retrospectively studied 36 carriers from 18 families evaluated at two Spanish hereditary cancer units (2005-2023). Clinical data were obtained from medical records, and variants were functionally classified using the Giacomelli model and IARC thresholds as dominant-negative with loss of function (DNE_LOF), non-dominant-negative without loss of function (noDNE_noLOF), non-dominant-negative with loss of function, or not assessed. Descriptive statistics summarized the tumor spectrum and group comparisons were performed using the Mann-Whitney U test (α = 0.05). Overall, 23 of 36 carriers (63.9%) developed at least one malignancy; 58.3% were female and the median age at first cancer was 36 years (range 27-54). Patients identified through MGP testing had later onset compared with those meeting clinical LFS criteria (median 42 [37-58] versus 27 [4-30] years; p = 0.011). Breast cancer was the most frequent tumor (65% of first cancers, median age 37 [30-47]), whereas none of the MGP-ascertained carriers developed LFS \"core\" tumors (sarcoma, brain tumor, adrenocortical carcinoma). Fifteen distinct germline variants were identified; 80% were missense, mainly in exons 5-8. DNE_LOF (median 30 [25-38.5]) were associated with earlier onset compared with noDNE_noLOF (47 [37-63]; p = 0.034). Eight carriers (34.7%) developed second primaries after a median interval of 6 years, and four developed third primaries. Functional classification may contribute to risk stratification; however, these findings are exploratory and hypothesis-generating, and require validation in larger prospective cohorts.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why patient organizations are important to improve care for people with Lynch syndrome.","authors":"Jurgen Seppen","doi":"10.1007/s10689-026-00572-1","DOIUrl":"10.1007/s10689-026-00572-1","url":null,"abstract":"<p><p>Improving health care requires patient involvement. For people with Lynch syndrome, general and specific areas can be identified in which it is important for health care professionals to collaborate with patients to improve care. This collaboration is mutually beneficial; better care for the patients, reduction of work load and higher chance of funding of research proposals for health care professionals. Patient organizations are comprised of patients that are often more educated and motivated to participate in discussions and workshops. In addition, patient organizations have access to a network of patients that can provide a broad overview of the needs and requirements of this group. Thus, patient organizations are the partners of choice in the collaboration of health care providers and patients. In this commentary, I outline the areas in which physicians and patients should collaborate; Providing information, research and clinical trial design, and psychological care and peer support.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13190412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971521","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":"Personalized risk estimates of advanced neoplasia development in individuals with a family history of colorectal cancer.","authors":"Marjolein J E Greuter, Eddymurphy U Akwiwu, Simone D Hennink, Tanya M Bisseling, Marcel B W Spanier, Iris D Nagtegaal, Karen Canfell, Evelien Dekker, Thomas Klausch, Iris Lansdorp-Vogelaar, Monique E van Leerdam, Nicoline Hoogerbrugge, Veerle M H Coupé","doi":"10.1007/s10689-026-00565-0","DOIUrl":"10.1007/s10689-026-00565-0","url":null,"abstract":"<p><p>To optimize surveillance in individuals with a family history (FH) of colorectal cancer (CRC), knowledge on the incidence rate of non-advanced adenomas (nAAs) and their progression rate to advanced neoplasia (AN) is crucial. We jointly estimated personalized adenoma incidence and progression rates using a novel statistical approach. We used data of individuals with ≥ 1 first-degree relative with CRC who underwent  ≥ 2 colonoscopies (n = 876 individuals; n = 2384 colonoscopies). Interval-censored data on timing and yield (no adenomas/nAA/AN) of each colonoscopy were available. nAA incidence and progression time from nAA to AN were estimated using a Bayesian progressive three-state model. Over a median follow-up of 6 years (interquartile range 5-6), 60 (6.8%) individuals developed AN (2 CRC, 58 AA) while 246 (28.1%) developed a nAA. The 5-year risk of developing nAA from baseline was estimated to be 29% (95% Crl: 21-39%). This risk was significantly associated with age and FH type. Estimated risk of progressing to AN within 5 years since nAA onset was 29% (95% Crl: 21-39%), and was significantly associated with having advanced adenomas at baseline. This resulted in a 5-year risk of transitioning from 'no adenomas' to AN of 7% (95% Crl: 5-9%). We showed that only 7% of individuals develop AN (primarily AAs) within the current 5-year colonoscopy surveillance interval. Future studies should evaluate whether this relatively low risk justifies slight extension of the surveillance interval or the use of fecal testing to guide colonoscopy timing. Furthermore, surveillance intensity could potentially be tailored based on age and FH.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13175997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940617","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":"Impaired glucose tolerance in women with BRCA1 versus BRCA2 pathogenic or likely pathogenic variants: Results from a prospective cohort study.","authors":"Giovanni Grandi, Claudia Piombino, Giovanna Sighinolfi, Elena Barbieri, Marta Venturelli, Chiara Melotti, Rebecca Lippi Bruni, Valentina Grisendi, Riccardo Cuoghi Costantini, Mina Grippa, Emma Zattarin, Elena Tenedini, Elisabetta Razzaboni, Giulia Brigante, Roberto D'Amico, Benedetta Nanni, Renata Menozzi, Laura Cortesi, Massimo Dominici, Antonio La Marca, Angela Toss","doi":"10.1007/s10689-026-00570-3","DOIUrl":"10.1007/s10689-026-00570-3","url":null,"abstract":"<p><strong>Background: </strong>Estrogens exert a beneficial effect on metabolism. Women carrying BRCA likely pathogenic/pathogenic variants (LP/PV) are at increased risk of premature menopause and may therefore be at higher risk of developing metabolic disorders later in life. In this single-center prospective cohort study, we investigated whether the specific BRCA mutation (BRCA1 vs. BRCA2) has a differential impact on metabolism in women.</p><p><strong>Methods: </strong>Eligible participants were BRCA LP/PV carriers who were premenopausal or underwent menopause -either natural or iatrogenic- within the 5 years prior to enrollment. Blood samples for lipid and glucose panels were obtained every 6 months, for a total of four time points. Body composition variables were evaluated at baseline and at the final follow-up using bioimpedance analysis. Glucose tolerance was assessed using the homeostatic model assessment for insulin resistance (HOMA-IR). Associations between lipid and glucose profile and patient characteristics were evaluated using univariable and multivariable linear regression models.</p><p><strong>Results: </strong>Fifty-seven BRCA1 and 58 BRCA2 LP/PV carriers were included in the final analysis. At baseline, BRCA1 LP/PV carriers had a higher body mass index (BMI) (27.3 vs. 24.6 kg/m², p = 0.01) and higher fat mass (27.3 vs. 21.9 kg, p = 0.013) than BRCA2 LP/PV carriers. Insulin levels and HOMA-IR were consistently higher in BRCA1 than in BRCA2 LP/PV carriers at all time points, and this difference was not attributable to age, BMI, menopausal status, risk-reducing salpingo-oophorectomy, previous chemotherapy or use of cholesterol-lowering agents. The lipid profile was similar between the groups, although BRCA1 LP/PV carriers showed a tendency toward a less favorable profile (higher LDL and lower HDL).</p><p><strong>Conclusions: </strong>These prospective results suggest that BRCA1 LP/PV carriers might have impaired glucose tolerance and a greater tendency toward insulin resistance compared with BRCA2 LP/PV carriers: this first report needs further independent confirmations from other cohorts.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940601","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":"Factors influencing uptake of risk-reducing mastectomy among unaffected Israeli BRCA1/BRCA2 pathogenic variant carriers.","authors":"Yael Laitman, Karin Aharon, Talia Schloss, Libby Margolin, Eitan Friedman","doi":"10.1007/s10689-026-00568-x","DOIUrl":"10.1007/s10689-026-00568-x","url":null,"abstract":"<p><p>Women harboring pathogenic variant (PV) in the BRCA1 or BRCA2 genes (= BRCA) have an elevated lifetime risk for breast cancer (BC). One of the main options for active BC risk reduction is bilateral risk-reducing mastectomy (RRM). Understanding the factors influencing that decision is important for genetic-counselling and risk mitigation strategy planning. A structured questionnaire was circulated to BRCA carriers, members of the Good Genes NGO in Israel. Data on RRM uptake and timing, factors previously reported to be associated with decision to undergo RRM (e.g., psychosocial, family history, counselling/health-system factors) were obtained. Comparison between carriers who elected to undergo RRM with those who opted for early detection schemes were performed using logistic regression and chi square statistical analyses. Of cancer free women (n = 391), 272 (69.6%) elected to adhere to the recommended surveillance scheme and 119 (30.4%) elected to undergo RRM. The major reasons for electing RRM over surveillance were active BC risk reduction (4.96 ± 0.23), fear of developing BC (4.86 ± 0.50), and having at least one relative with BC diagnosed under age 45 years. Support group discussions emerged as a stronger determinant of RRM uptake than primary care physician or religious guidance. In conclusion, among healthy Israeli BRCA carriers the decision to undergo RRM was influenced by a complex interplay of factors-active BC risk reduction, fear of cancer diagnosis in the context of having one relative with early onset BC and support group discussions were the major drivers of RRM in Israeli BRCA1 carriers.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927483","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 breast cancer, pancreatic cancer, and melanoma in a CDKN2A variant common in the Hispanic population.","authors":"Emily S Parkhurst, Jaime L Natoli, Xing Wei, Darwin A Luna, Timothy J Maarup","doi":"10.1007/s10689-026-00569-w","DOIUrl":"10.1007/s10689-026-00569-w","url":null,"abstract":"<p><p>Pathogenic and likely pathogenic variants (P/LP) in the CDKN2A gene are associated with melanoma-pancreatic cancer susceptibility syndrome. The lifetime risk for melanoma is estimated to be 28-76%, while the lifetime risk of pancreatic cancer is > 15%. A common CDKN2A variant in the Hispanic population, c.146 T > C, has conflicting interpretations of pathogenicity, with some laboratories calling this variant LP and others calling it uncertain significance (VUS), which leads to inconsistent clinical recommendations for cancer screening. The objective of this study was to determine if there is an association between the CDKN2A c.146 T > C variant and melanoma, pancreatic cancer, and/or breast cancer. We conducted a retrospective cohort study of the Southern California Kaiser Genetics Hereditary Cancer Database from January 2013 to January 2024. We determined the presence of melanoma, pancreatic cancer, and breast cancer among 202 individuals with the CDKN2A c.146 T > C variant (\"c.146 T > C group\") and compared them to 190 individuals with Hispanic ancestry and a negative germline panel (\"negative control group\") as well as 53 individuals with a CDKN2A P/LP variant other than c.146 T > C (\"positive control group\"). Multiple logistic regression was utilized to produce adjusted odds ratios (aOR), 95% confidence intervals (CI), and p-values. The adjusted odds of melanoma (aOR 6.1, 95% CI 1.3 to 27.9), pancreatic cancer (aOR 13.9, 95% CI 1.7 to 113.4), and breast cancer (aOR 3.2, 95% CI 1.8 to 5.6) were significantly higher in the c.146 T > C group compared to the negative control group. When the c.146 T > C group was compared to the positive control group, the adjusted odds of melanoma (aOR 0.9, 95% CI 0.1 to 8.0), pancreatic cancer (aOR 12.2, 95% CI 0.3 to 511.4), and breast cancer (aOR 1.9, 95% CI 0.4 to 8.4) were not significantly different. Although CDKN2A c.146 T > C is a relatively common variant in the Hispanic population, our data shows it may confer cancer risks similar to other CDKN2A P/LP variants. Increased risk of breast cancer has previously been reported with CDKN2A leading to questions about whether the increased breast cancer risk seen in this study is variant specific. Given the prevalence of this variant in an underserved population, our results suggest that the risks of cancer associated with this Hispanic variant warrant counseling and clinical follow-up.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial risks in prostate cancer between brothers and half-brothers as clues to germline genetic and environmental causes.","authors":"Kari Hemminki, Frantisek Zitricky, Kristina Sundquist, Jan Sundquist, Asta Försti, Akseli Hemminki, Otto Hemminki","doi":"10.1007/s10689-026-00562-3","DOIUrl":"10.1007/s10689-026-00562-3","url":null,"abstract":"<p><p>Swedish family and cancer data constitute the largest source on familial cancer in the world. We analyze here familial risks in prostate cancer (PC) with focus on multiple affected brothers and comparation of full-brothers to maternal and paternal half-brothers. Age-specific incidence and standardized incidence ratios (SIRs) were calculated for PC in brothers. Curves for relative risk (RR) by diagnostic age were plotted for risk distributions. A total of 115,066 PCs were diagnosed in 1.2 million men. Familial SIR for full brothers was 2.23, for maternal half-brothers it was 1.92 and paternal half-brothers was 1.34. Considering SIRs with least possible detection bias (7+ years after first brother's diagnosis) the above SIRs were 2.06, 1.66 and 1.41. SIRs in full brothers increased stepwise by the number of affected brothers reaching 21.33 when 6 brothers were affected. Age-RR curves for two affected brothers declined evenly from RR 2.8 at age 45 to below 2.0 at age 80. When four or more brothers were affected, a discrete high-risk peak (RR 4-7) was detected between ages 60 and 69. Data on full-brothers and half-brothers indicate that familial risk in PC is largely genetic which is also supported by discrete RR peaks in high-risk families at ages matching preferential penetrance age for known predisposition genes of PC. Familial risk increased already when two brothers were affected calling for clinical vigilance concerning family history. Family history should deserve a place as an inclusion criterium in schemes for PC screening.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866685","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":"Optimal upper gastrointestinal surveillance strategies for gastric, small bowel and pancreatic cancer detection in Lynch syndrome.","authors":"Tim Marwitz, Aleksander M Bogdanski, Robert Hüneburg, Monique E van Leerdam","doi":"10.1007/s10689-026-00567-y","DOIUrl":"10.1007/s10689-026-00567-y","url":null,"abstract":"<p><p>Lynch syndrome is an autosomal dominant cancer predisposition syndrome and the most common cause of hereditary colorectal cancer. In addition to colorectal cancer, it confers substantially increased risks for several extracolonic malignancies. While there is broad consensus regarding the effectiveness of endoscopic colorectal surveillance, recommendations for surveillance of gastric, small bowel, and pancreatic cancers vary considerably among guidelines issued by leading professional societies. These discrepancies largely reflect the limited availability of robust, high-quality evidence. In this narrative review, we summarize the cancer risks for gastric, small bowel, and pancreatic malignancies in Lynch syndrome carriers, discuss recent studies evaluating the outcomes of surveillance strategies, and provide an overview of current guideline recommendations. Furthermore, we highlight emerging approaches that may enhance surveillance strategies in the future. In recent years, increasing research efforts have focused on surveillance for less frequent Lynch syndrome-associated malignancies, however, prospective data from large, well-characterized cohorts remain scarce. Such data are essential to harmonize existing guidelines and to enable the development of personalized surveillance strategies for individuals affected by Lynch syndrome.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867191","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":"Biallelic germline MBD4 mutations predispose to colorectal polyposis, hypermutated AML, and schwannomas.","authors":"Julia Cooper, Brittany L Stewart, Lauren Bokovitz, Hetty Carraway, Sudipto Mukherjee, David Liska, Sumithira Vasu, Harry Lesmana, James S Blachly","doi":"10.1007/s10689-026-00566-z","DOIUrl":"10.1007/s10689-026-00566-z","url":null,"abstract":"<p><p>Biallelic pathogenic variants in the MBD4 gene have recently been associated with an autosomal recessive cancer predisposition syndrome deemed \"MBD4-associated neoplasia syndrome (MANS)\". Early reports of individuals with MANS highlight the propensity to develop young onset colorectal polyposis and hyper-mutated acute myeloid leukemia (AML). In the following case series, we present four patients with MANS from three families with polyps and AML, as well as additional features previously less described, such as schwannoma and thyroid cancer. This series increases the total number of reported cases by 27%, with the intention of achieving a more robust understanding of the full phenotypic spectrum of MANS.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835782","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":"Lynch syndrome integrative epidemiology and genetics (LINEAGE): rationale for cohort design.","authors":"Swati G Patel, Holli A Loomans-Kropp, Zachariah H Foda, Bryson W Katona, Suzi Birz, Carol A Burke, Jordan Clawson, Brian Furner, Camille Hochheimer, Elizabeth Magnan, Luigi Ricciardiello, Harminder Singh, Samuel Volchenboum, Michael Watkins, Timothy Yen, Mohammad Abbass, Nicholas J Bartell, Beth Dudley, Luke Engelking, Jose Guillem, Robert Hollis, Gregory Idos, Blake A Jones, Priyanka Kanth, Fay Kastrinos, Dan Li, Aimee L Lucas, Gautam N Mankaney, Jennifer K Maratt, Danielle Marino, Joshua Melson, Long H Nguyen, Kavya M Reddy, Kasmintan A Schrader, Rachel Silva-Smith, Aparajita Singh, Peter P Stanich, Elena M Stoffel, Sapna Syngal, Jennifer M Weiss, Matthew B Yurgelun, Dana Zakalik, Samir Gupta, Ajay Bansal, Sonia S Kupfer","doi":"10.1007/s10689-026-00552-5","DOIUrl":"10.1007/s10689-026-00552-5","url":null,"abstract":"<p><strong>Background: </strong>The Lynch syndrome INtegrative Epidemiology And GEnetics (LINEAGE) consortium was established to address gaps in understanding genotype-specific cancer risks and risk-modifiers in contemporary North American Lynch syndrome (LS) populations. LINEAGE is a multi-center, longitudinal cohort to systematically collect data on risk factors, adherence to care, quality of surveillance, and patient-, provider-, and system-level factors associated with incident LS-associated cancers.</p><p><strong>Methods: </strong>LINEAGE recruits individuals with confirmed pathogenic or likely pathogenic variants in LS-associated genes from participating institutions. Data includes retrospective and prospective collection, encompassing clinical abstraction (demographics, surgical history, endoscopic data, treatments), patient-reported surveys (behavioral/lifestyle factors, quality of life, procedures), endoscopist-level data, and biosample metadata. A standardized REDCap database, data harmonization protocols, and a virtual biobank support reproducibility and linkage of clinical data and biosamples. Rigorous quality assurance/quality control processes are embedded for data integrity.</p><p><strong>Results: </strong>Participating centers will contribute data to determine gene-specific risks, and gene-environment interactions for Lynch-associated, and other cancers. We will evaluate associations with exposure to, and quality of cancer risk-reduction care, including endoscopic surveillance, risk-reduction surgery, and chemoprevention. The inclusion of provider-level variables, such as endoscopist training and experience, enables unique research into modifiers of post-endoscopy cancer risk. The linked biosample resources will further facilitate mechanistic studies and biomarker discovery.</p><p><strong>Conclusions: </strong>LINEAGE provides a robust platform for advancing LS research by integration of clinical, pathological, epidemiological and genetic data across institutions. Its standardized, collaborative framework enhances the validity and generalizability of risk estimates that will guide decision-making and policy for surveillance to ultimately reduce morbidity and mortality for individuals with Lynch syndrome.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":"25 2","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}