ArticleJAMA2006
Prediction of MLH1 and MSH2 mutations in Lynch syndrome.
Article in JAMA, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 3 syntheses or guidelines pooled it, 191 citations in OpenAlex.
- Prevalence of pathological germline mutations of hMLH1 and hMSH2 genes in colorectal cancer.PloS one · 2013Pooled it
- Guidelines for biomarker testing in colorectal carcinoma (CRC): a national consensus of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2012Guideline
- SEOM clinical guidelines for hereditary cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2011Guideline
- Diet-Driven Epigenetic Alterations in Colorectal Cancer: From DNA Methylation and microRNA Expression to Liquid Biopsy Readouts.Biomedicines · 2026Review
- Comparison of PREMM5 and PREMMplus Risk Assessment Models to Identify Lynch Syndrome.JCO precision oncology · 2025Article
- Development and Validation of a Prediction Model for Failure of the Transfemoral Approach of Endovascular Treatment for Large Vessel Occlusion Acute Ischemic Stroke.Cerebrovascular diseases (Basel, Switzerland) · 2024Article
- Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer.Human genomics · 2023Article
- Development and evaluation of INTFrontiers in oncology · 2023Article
- Updates in gynecologic care for individuals with lynch syndrome.Frontiers in oncology · 2023Review
- A validation of models for prediction of pathogenic variants in mismatch repair genes.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- PREDICTION OF HEREDITARY CANCERS USING NEURAL NETWORKS.The annals of applied statistics · 2022Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- miRGTF-net: Integrative miRNA-gene-TF network analysis reveals key drivers of breast cancer recurrence.PloS one · 2021Article
- Hereditary Predisposition to Prostate Cancer: From Genetics to Clinical Implications.International journal of molecular sciences · 2020Review
- Economic Burden of Depression and Associated Resource Use in Manitoba, Canada.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2020Article
- Lynch Syndrome Germline Mutations in Breast Cancer: Next Generation Sequencing Case-Control Study of 1,263 Participants.Frontiers in oncology · 2020Article
- Effective Identification of Lynch Syndrome in Gastroenterology Practice.Current treatment options in gastroenterology · 2019Review
- Community Practice Implementation of a Self-administered Version of PREMMClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2018Article
- Prevalence and clinicopathologic/molecular characteristics of mismatch repair-deficient colorectal cancer in the under-50-year-old Japanese population.Surgery today · 2017Article
- Development and Validation of the PREMMJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
contextLynch syndrome is caused primarily by mutations in the mismatch repair genes MLH1 and MSH2.
objectivesTo analyze MLH1/MSH2 mutation prevalence in a large cohort of patients undergoing genetic testing and to develop a clinical model to predict the likelihood of finding a mutation in at-risk patients. DESIGN, SETTING, AND
participantsPersonal and family history were obtained for 1914 unrelated probands who submitted blood samples starting in the year 2000 for full gene sequencing of MLH1/MSH2. Genetic analysis was performed using a combination of sequence analysis and Southern blotting. A multivariable model was developed using logistic regression in an initial cohort of 898 individuals and subsequently prospectively validated in 1016 patients. The complex model that we have named PREMM(1,2) (Prediction of Mutations in MLH1 and MSH2) was developed into a Web-based tool that incorporates personal and family history of cancer and adenomas.
main outcome measureDeleterious mutations in MLH1/MSH2 genes.
resultsOverall, 14.5% of the probands (130/898) carried a pathogenic mutation (MLH1, 6.5%; MSH2, 8.0%) in the development cohort and 15.3% (155/1016) in the validation cohort, with 42 (27%) of the latter being large rearrangements. Strong predictors of mutations included proband characteristics (presence of colorectal cancer, especially > or =2 separate diagnoses, or endometrial cancer) and family history (especially the number of first-degree relatives with colorectal or endometrial cancer). Age at diagnosis was particularly important for colorectal cancer. The multivariable model discriminated well at external validation, with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval, 0.76-0.84).
conclusionsPersonal and family history characteristics can accurately predict the outcome of genetic testing in a large population at risk of Lynch syndrome. The PREMM(1,2) model provides clinicians with an objective, easy-to-use tool to estimate the likelihood of finding mutations in the MLH1/MSH2 genes and may guide the strategy for molecular evaluation.
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