[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"mlh1-gene-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:mlh1-gene-mutation":33},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,79,106,137,161],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":23,"conditions":24,"keywords":47,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":69,"startDateStruct":72,"completionDateStruct":74,"leadSponsor":76,"locationsCount":5},"100570529","lynch-syndrome-x-talk-of-enteral-mucosa-with-immune-system-100570529",false,"NCT06708429","Lynch Syndrome X-Talk of Enteral Mucosa With Immune System","Impact of Immune-surveillance on the Development of Colorectal Cancer in Patients With Lynch Syndrome","LYNX-EYE","Inclusion Criteria (for participants with Lynch syndrome):\n\n* Age ≥18 years\n* All sexes eligible\n* Established diagnosis of Lynch syndrome performed as part of clinical practice, with a germline pathogenic\u002Flikely pathogenic variant in one of the following genes: MLH1, MSH2, MSH6, PMS2, and EpCAM\n* Subjects with Lynch syndrome undergoing surveillance gastrointestinal endoscopy and\u002For surgery according to clinical practice\n* Fertile patients (both males and females) are eligible\n* Lactating women are eligible\n\nInclusion Criteria (for participants without Lynch syndrome):\n\n* Age ≥18 years\n* All sexes eligible\n* Patients with sporadic colorectal lesions, including colorectal cancer and colorectal adenomas\n* Healthy controls without colorectal cancer or adenomas undergoing lower gastrointestinal endoscopy for abdominal pain\n* PREMM5 \\\u003C 2.5 \\[PREMM5 is an online, free-to-use, clinical prediction algorithm that estimates the cumulative probability of an individual carrying a germline mutation in the mismatch repair genes responsible for Lynch syndrome\\].\n\nExclusion Criteria (for participants with or without Lynch syndrome):\n\n* Age \\\u003C 18 years;\n* Diseases that are known to predispose to colorectal cancer (personal past or recent history of inflammatory bowel disease);\n* Patients unable\u002Funwilling to provide consent;\n* Pregnancy","ALL","18 Years",{"count":20,"type":21},300,"ESTIMATED","OBSERVATIONAL","Lynch syndrome (OMIM #120435) is the most common dominantly inherited colorectal cancer syndrome with an estimated prevalence of 1:270 individuals. It increases the lifetime risk of colorectal and endometrial cancer primarily, but it is associated with a high risk of other cancers (pancreas, stomach, ovarian, central nervous system, skin, among others). It is caused by a germline mutation in one of four DNA mismatch repair genes or a terminal deletion of the MSH2-adjacent gene EpCAM.\n\nDespite adherence to cancer surveillance programs, many patients still develop colorectal cancer and endometrial cancer. The Prospective Lynch Syndrome Database (PLSD) suggests that more frequent surveillance intervals do not significantly improve cancer risk reduction. The PLSD also revealed that the incidence of colorectal cancer in MLH1 and MSH2 carriers was even higher than previously expected, reaching as high as 41-36% among MLH1 carriers, regardless of ethnic background. The development of colorectal cancer despite surveillance is an unresolved question. Therefore, there is an unmet need for effective cancer prevention strategies.",[25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46],"Lynch Syndrome","Lynch Syndrome I","Lynch Syndrome II","Lynch Syndrome I (Site-specific Colonic Cancer)","HNPCC","HNPCC Gene Mutation","Hereditary Cancer Syndrome","Hereditary Cancer","MLH1 Gene Mutation","MLH1 Gene Deletion+Duplication","MLH1 Loss of Expression","MLH1 Gene Inactivation","MSH2 Gene Mutation","MSH2 Gene Deletion+Duplication","MSH2 Loss of Expression","MSH2 Gene Inactivation","MSH6 Gene Mutation","MSH6 Loss of Expression","MSH6 Gene Inactivation","PMS2 Gene Mutation","PMS2 Gene Inactivation","PMS2 Loss of Expression",[48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66],"Colorectal cancer","Endometrial cancer","Lynch syndrome-associated cancer","Surveillance","Cancer surveillance","Immune profile","Immune escape","Mismatch repair deficiency","Microbiota","Liquid biopsy","MicroRNA","Transcriptomic","Frame shift peptides","MLH1","MSH2","EpCAM","MSH6","PMS2","Hair matrix","RECRUITING","2026-04-21",{"date":70,"type":71},"2026-04-24","ACTUAL",{"date":73,"type":71},"2023-06-01",{"date":75,"type":21},"2034-06-01",{"name":77,"class":78},"San Raffaele University","OTHER",{"id":80,"slug":81,"hasResults":11,"nctId":82,"briefTitle":83,"officialTitle":84,"acronym":4,"eligibilityCriteria":85,"healthyVolunteers":86,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":87,"targetDuration":4,"studyType":89,"phases":90,"briefSummary":92,"conditions":93,"keywords":95,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":98,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":105},"100493350","videocapsule-endoscopy-in-lynch-syndrome-100493350","NCT05704010","Videocapsule Endoscopy in Lynch Syndrome","Role of Videocapsule Endoscopy in Lynch Syndrome: a Multicenter Italian Registry Study","Inclusion Criteria:\n\n* Pathogenic germline variant in one of the MMR genes (MLH1, MSH2\u002FEpcam, MSH6, or PMS2).\n\nExclusion Criteria:\n\n* Patients younger than 18 years of age\n* Patients unwilling or unable to provide informed consent\n* Patients with prior small bowel surgery\n* Patients with a contraindication to VCE",true,{"count":88,"type":21},100,"INTERVENTIONAL",[91],"NA","Background Lynch syndrome is caused by a pathogenic variant in one of the four Mismatch Repair genes (MMR): MLH1, MSH2\u002FEpcam, MSH6, or PMS2. These pathogenic variants confer a higher risk of developing colorectal and other cancers, including small bowel cancer. The risk of developing a small bowel adenocarcinoma is about 100 times higher compared to individuals without Lynch syndrome, and the lifetime risk of small bowel cancer is estimated at 4,2%.\n\nThe diagnosis of a small bowel cancer depends on videocapsule endoscopy (VCE). This device is swalled so that it can record images of the small bowel, which are then stored on a wearable device for about 8 hours. The capsule is then expelled in the feces while the images are transferred to a computer to be analysed. To date, there is conflicting evidence on the efficacy of small bowel cancer screening with VCE\n\nRationale: this registry study will collect prospective data from patients with LS undergoing VCE\n\nAim: evaluate the incidence of neoplastic and pre-neoplastic lesions in patients with LS during a VCE-based small bowel cancer screening study\n\nDesign: this is a multicentric, observational study that analyzes data from diagnostic techniques already approved. Patients will not undergo diagnostic procedures beyond what would be recommended by clinical practice.",[25,26,27,33,37,41,44,94],"Small Bowel Adenocarcinoma",[96,97],"Videocapsule","Small bowel",{"date":99,"type":71},"2026-04-22",{"date":101,"type":71},"2018-11-01",{"date":103,"type":21},"2029-12-31",{"name":77,"class":78},1,{"id":107,"slug":108,"hasResults":11,"nctId":109,"briefTitle":110,"officialTitle":110,"acronym":111,"eligibilityCriteria":112,"healthyVolunteers":86,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":113,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":115,"conditions":116,"keywords":4,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":128,"lastUpdatePostDateStruct":129,"startDateStruct":131,"completionDateStruct":133,"leadSponsor":135,"locationsCount":136},"100627590","liquid-biopsy-and-machine-learning-for-early-colorectal-cancer-adenomas-lynch-cancers-and-residual-disease-detection-100627590","NCT07450612","Liquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection","BEACON","Inclusion Criteria:\n\n* All individuals included in the study need to have had a colonoscopy at the time of blood sampling.\n* Received standard diagnostic and staging (as necessary) procedures as per local guidelines, and at least one sample was drawn before receiving any curative-intent treatment.\n* Received standard pathological and endoscopic diagnosis and assessment for cohort assignment\n\nExclusion Criteria:\n\n* Lack of informed consent\n* Inflammatory bowel disease",{"count":114,"type":21},1200,"This is an multicenter study that will test the diagnostic accuracy of a blood test (i.e., a liquid biopsy) for the diagnosis of colorectal cancer (CRC), advanced adenomas (AAs), as well as Lynch-syndrome associated cancers. Additionally, a pre-planned analysis will evaluate the use of this liquid biopsy as a tool for molecular residual disease monitoring purposes.",[117,118,119,120,121,122,123,25,26,27,28,124,125,126,33,37,41,44,127],"Colorectal Cancer","Adenoma Colon","Adenoma Colon Polyp","Colon Adenoma","Colo-rectal Cancer","Colon Disease","Colon Neoplasm","LYN Gene Mutation","Mismatch Repair Deficiency","Mismatch Repair Gene Mutation","EPCAM Gene Mutation","2026-02-27",{"date":130,"type":71},"2026-03-04",{"date":132,"type":71},"2024-01-01",{"date":134,"type":21},"2031-08-15",{"name":77,"class":78},4,{"id":138,"slug":139,"hasResults":11,"nctId":140,"briefTitle":141,"officialTitle":142,"acronym":143,"eligibilityCriteria":144,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":145,"targetDuration":4,"studyType":22,"phases":4,"briefSummary":147,"conditions":148,"keywords":4,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":152,"lastUpdatePostDateStruct":153,"startDateStruct":155,"completionDateStruct":157,"leadSponsor":159,"locationsCount":105},"100591618","how-epigenetic-changes-in-hmlh1-connect-lab-research-with-diagnosis-in-gastric-cancer-100591618","NCT06982768","How Epigenetic Changes in hMLH1 Connect Lab Research With Diagnosis in Gastric Cancer","Epigenetic Mechanisms Bridging Research and Clinical Examination in hMLH1 Hypermethylated Gastric Cancer","EMBRACE-hGC","Inclusion Criteria:\n\n* Patients who underwent elective gastrectomy for Stage I-IV gastric cancer.\n* Surgery performed at the General Surgery Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS.\n* Procedures conducted between January 2017 and August 2023.\n* Only patients who have already undergone immunohistochemistry evaluation for expression of the components of the MMR complex (MLH1, PMS2, MSH2, and MSH6).\n\nExclusion Criteria:\n\n\\- Patients with missing immunohistochemistry evaluation for the expression of the components of the MMR complex (MLH1, PMS2, MSH2, and MSH6).",{"count":146,"type":21},245,"DNA methylation is one of the key mechanisms that are thought to underlie the association between aging and cancer. Several methylation-based measures of biological aging have been developed and have demonstrated an association with mortality and, in some cases, with cancer incidence. Accordingly, CpG promoter hypermethylation is a well-known mechanism of gene inactivation in carcinogenesis.\n\nGastric cancer has been classified in different molecular phenotypes based on genetic and epigenetic characteristics. One of these subtypes is characterized by a high grade of microsatellite instability (MSI-H). In gastric cancer, the MSI-H status is mostly caused by methylation of the hMLH1 gene promoter (between 71% and 78%), that is also considered the representative of a gastric-specific CpG island methylation pattern (CIMP). Gastric cancer with hMLH1 hypermethylation is frequently expressed in the MSI-H phenotype but also reported in the MSI-L type. Hypermethylation has been associated with advanced age, dietary habits, smoking and alcohol consumption. Moreover, other studies on GI cancer (colorectal, rectal and gastric) have associated hMLH1 hypermethylation with decreased levels of folate, vitamin C and niacin. Last, increased oxidative stress has been proposed as one of the possible initiators of cancer development and progression through epigenetic mechanism as hypermethylation. From a clinical standpoint, MSI-H gastric cancers have been associated with increased resistance to standard chemotherapy and increased immunogenicity, representing a hypothetic ideal target to immunotherapy, that has documented clinical efficacy for this subtype. However, some authors have suggested that MSI-H GCs without hMLH1 hypermethylation and GCs with hMLH1 hypermethylation could be different in terms of clinicopathologic characteristics and biological behavior. In addition, the specific role of hMLH1 hypermethylation in resistance to standard chemotherapy is unknown, as well as its potential adjunctive role in the chemoresistance of hypermethylated - but MSI-L - tumors.\n\nIdentifying risk factors for hMLH1 hypermethylated GC could have relevant implications in terms of disease prevention and even reversal of the hypermethylation mechanisms through natural as well as synthetic compounds. It could also identify a predictive tool to better stratify patients for expected sensitivity to specific chemotherapy (or biological therapy) regimens. Therefore, this preliminary study aims to determine if the development of hMLH1-methylated GC is associated with specific clinicopathologic characteristics and environmental habits. It also aims to report on the biological behavior of these tumors, as well as on their chemosensitivity to platin-based chemotherapy regimens.",[149,150,33,151],"Gastrectomy for Gastric Cancer","Gastrectomy","Gastric Cancer","2025-12-29",{"date":154,"type":71},"2026-01-02",{"date":156,"type":71},"2024-09-01",{"date":158,"type":21},"2026-04-30",{"name":160,"class":78},"Fondazione Policlinico Universitario Agostino Gemelli IRCCS",{"id":162,"slug":163,"hasResults":11,"nctId":164,"briefTitle":165,"officialTitle":166,"acronym":4,"eligibilityCriteria":167,"healthyVolunteers":86,"sex":17,"minAge":168,"maxAge":4,"enrollmentInfo":169,"targetDuration":4,"studyType":89,"phases":171,"briefSummary":172,"conditions":173,"keywords":191,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":196,"lastUpdatePostDateStruct":197,"startDateStruct":199,"completionDateStruct":201,"leadSponsor":203,"locationsCount":204},"100471529","an-intervention-to-increase-genetic-testing-in-families-who-may-share-a-gene-mutation-related-to-cancer-risk-and-an-intervention-to-help-patients-and-their-primary-care-providers-stay-up-to-date-about-uncertain-genetic-test-results-100471529","NCT05420064","An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results","Digital Technology to Enhance Access to and Effectiveness of Cancer Genetic Counseling: Effective Familial OutReach Via Tele-genetics (EfFORT) Trial & Supporting Test Result Interpretation and Variant Education (STRIVE) Trial","Inclusion Criteria:\n\nEfFORT Trial Probands\n\n* Current MSK patient\n* Received post-test genetic counseling from MSK Clinical Genetics Service within the last 3 months (or within the last year for the de-identified non-randomized control probands)\n* 25 years of age or older\n* Self-reported \"very well\" comprehension of written and verbal English language or Spanish language\n* Has at least one ARR who meets criteria for study enrollment (see below)\n* First in the family to test positive for PV at MSK in any of the following cancer susceptibility genes, or an ARR of an MSK proband who converted to the proband role:\n\nAPC I1307K, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDKN2A (P16), CHEK2, EPCAM, GREM1, MLH1, MSH2, MSH6, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, BAP1, DICER1, FH, FLCN, HOXB13, KIT, MAX, MEN1, MET, MITF, PTCH1, RAD51B, RET, SDHB, SDHC, SDHD, STK11, SUFU, TMEM127, TSC1, TSC2, VHL\n\nPrincipal Investigator discretion will be used to determine whether specific variants within the above genes meet a clinical actionability threshold to warrant familial genetic testing.\n\nEfFORT Trial At-Risk Relatives (ARRs):\n\n* Biological first-, second-, or third- degree relative of enrolled MSK proband\n* 25 years of age or older\n* Resides within the United States\n* Self-reported medical insurance which can be in or out of network with MSK\n* Self-reported \"very well\" comprehension of written and verbal English language\n\nSTRIVE Trial VUS Patients\n\n* Current MSK patient\n* Received post-test genetic counseling from MSK Clinical Genetics Service within the last 3 months\n* 25 years of age or older\n* Self-reported \"very well\" comprehension of written and verbal English language or Spanish language\n* Has a VUS identified in any of the following cancer predisposition genes:\n\nAPC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (P16), CHEK2, CTNNA1, DICER1, ELOC, EPCAM, FH, FLCN, GREM1, HOXB13, KEAP1, MAX, MBD4, MEN1, MET, MITF, MLH1, MLH3, MSH2, MSH3, MSH6, MUTYH, NF1, NF2, NTHL1, PALB2, PMS2, POLD1, POLE, POT1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RET, RNF43, RPS20, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, STK11, TERT, TMEM127, TP53, TSC1, TSC2, VHL\n\nSTRIVE Trial PCP Providers:\n\n* Designated healthcare provider for an enrolled VUS patient\n* Resides within the United States\n\nExclusion Criteria:\n\nEfFORT Trial Probands\n\n* Is unwilling or unable to provide informed consent\n* Is unwilling or unable to create a MyMSK patient portal account (see section 3.0 on MyMSK patient usage at MSK and CGS)\n* Does not have an email address\n* Has enrolled in the STRIVE trial\n\nEfFORT Trial At-Risk Relatives (ARRs):\n\n* Is unwilling or unable to provide informed consent\n* Is unwilling or unable to create a MyMSK patient portal account\n* Has previously undergone genetic testing for the familial PV\n* Does not have an email address\n* Has opted out of study contact\n\nSTRIVE Trial VUS Patients\n\n* Is unwilling or unable to provide informed consent\n* Is unwilling or unable to create a MyMSK patient portal account (see section 3.0 on MyMSK patient usage at MSK and CGS)\n* Does not have an email address\n* Has enrolled in the EfFORT trial\n\nSTRIVE Trial PCP Providers\n\n* Contact information not available","25 Years",{"count":170,"type":21},1000,[91],"The purpose of this study is to examine the impact of new cancer genetic counseling models that aim to increase patient engagement with the genetics team. To do this, the study consists of two trials to evaluate two related interventions. The first trial is the EfFORT Trial, which evaluates a cascade genetic testing intervention. Cascade testing is the process of offering genetic testing to people who are at risk of having inherited a possibly harmful gene change that has been found in their family. The study will look at how often genetic testing occurs when healthcare providers have permission to reach out to family members to recommend genetic testing and to help those who are interested get tested. The study will look at whether this cascade testing intervention is practical and effective. The study would like to see how this approach of healthcare providers reaching out directly to family members compares with the usual approach of patients telling their family members about the recommendation to get genetic testing. The second trial is the STRIVE Trial, which evaluates an intervention designed to help patients who receive an uncertain result from genetic testing (also called a \"variant of uncertain significance\") stay connected with their genetics care team, and to help patients and their primary care providers stay up-to-date about the meaning of uncertain genetic test results. The study will look at whether an intervention that consists of a study online portal for patients with uncertain genetic test results and their primary care providers will help them to stay up-to-date on the meaning of uncertain genetic test results. The study would like to see how this intervention compares to the usual approach of encouraging patients to re-contact their genetics care team on their own about a year after getting genetic testing.\"",[174,175,176,177,178,179,180,33,181,37,182,41,183,44,184,127,185,186,187,188,189,190],"BRCA1 Mutation","POLD1 Gene Mutation","CDKN2A Mutation","BRCA2 Mutation","POLE Gene Mutation","APC Gene Mutation","ATM Gene Mutation","BARD1 Gene Mutation","BRIP1 Gene Mutation","CHEK2 Gene Mutation","PALB2 Gene Mutation","RAD51C Gene Mutation","BMPR1A Gene Mutation","RAD51D Gene Mutation","SMAD4","PTEN Gene Mutation","GREM1",[192,193,194,195],"EfFORT","Memorial Sloan Kettering Cancer Center","Genetic Testing","22-023","2025-11-10",{"date":198,"type":71},"2025-11-12",{"date":200,"type":71},"2022-12-01",{"date":202,"type":21},"2026-11-30",{"name":193,"class":78},8]