ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2016
Clinicopathologic Risk Factor Distributions for MLH1 Promoter Region Methylation in CIMP-Positive Tumors.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Large-scale external validation and meta-analysis of gene methylation biomarkers in tumor tissue for colorectal cancer prognosis.EBioMedicine · 2024Pooled it
- The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Pooled it
- DNA methylation signatures of sporadic colorectal cancer with microsatellite instability.Epigenetics · 2026Article
- MLH1 promoter methylation in pancreatic ductal adenocarcinoma: frequent but not prognostic.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
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- Non-invasive colorectal cancer screening methods: focusing on diagnostic genetic and epigenetic markers.Cancer cell international · 2025Review
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- Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities.PLoS neglected tropical diseases · 2024Article
- Sex Difference of Colon Adenoma Pathway and Colorectal Carcinogenesis.The world journal of men's health · 2024Review
- Multiregional assessment of CIMP in primary colorectal cancers: Phenotype concordance but marker variability.International journal of cancer · 2021Article
- Association ofOncoimmunology · 2021Article
- Updates on Clinical Use of Liquid Biopsy in Colorectal Cancer Screening, Diagnosis, Follow-Up, and Treatment Guidance.Frontiers in cell and developmental biology · 2021Review
- Whole-exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast.Histopathology · 2019Article
- Impact of LINE-1 hypomethylation on the clinicopathological and molecular features of colorectal cancer patients.PloS one · 2018Article
- CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers.International journal of cancer · 2017Article
- The dynamic DNA methylation landscape of theClinical epigenetics · 2017Article
- Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.Oncotarget · 2016Article
- Molecular Biomarkers in the Personalized Treatment of Colorectal Cancer.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2016Review
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 3 countries.
Funding
Abstract
backgroundThe CpG island methylator phenotype (CIMP) is a major molecular pathway in colorectal cancer. Approximately 25% to 60% of CIMP tumors are microsatellite unstable (MSI-H) due to DNA hypermethylation of the MLH1 gene promoter. Our aim was to determine if the distributions of clinicopathologic factors in CIMP-positive tumors with MLH1 DNA methylation differed from those in CIMP-positive tumors without DNA methylation of MLH1.
methodsWe assessed the associations between age, sex, tumor-site, MSI status BRAF and KRAS mutations, and family colorectal cancer history with MLH1 methylation status in a large population-based sample of CIMP-positive colorectal cancers defined by a 5-marker panel using unconditional logistic regression to assess the odds of MLH1 methylation by study variables.
resultsSubjects with CIMP-positive tumors without MLH1 methylation were significantly younger, more likely to be male, and more likely to have distal colon or rectal primaries and the MSI-L phenotype. CIMP-positive MLH1-unmethylated tumors were significantly less likely than CIMP-positive MLH1-methylated tumors to harbor a BRAF V600E mutation and significantly more likely to harbor a KRAS mutation. MLH1 methylation was associated with significantly better overall survival (HR, 0.50; 95% confidence interval, 0.31-0.82).
conclusionsThese data suggest that MLH1 methylation in CIMP-positive tumors is not a completely random event and implies that there are environmental or genetic determinants that modify the probability that MLH1 will become methylated during CIMP pathogenesis. IMPACT: MLH1 DNA methylation status should be taken into account in etiologic studies.
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