ReviewInternational journal of cancer2011
Prognostic significance of CDKN2A (p16) promoter methylation and loss of expression in 902 colorectal cancers: Cohort study and literature review.
Review in International journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 9 of them syntheses that pooled it.
What it found
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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
85 citing papers in PubMed, 9 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data.Acta neuropathologica communications · 2023Pooled it
- Pooled it
- Prognostic and clinicopathological value of p16 protein aberrant expression in colorectal cancer: A PRISMA-compliant Meta-analysis.Medicine · 2018Pooled it
- Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.Clinical epigenetics · 2018Pooled it
- Pooled it
- Clinicopathological significance and potential drug target of RUNX3 in non-small cell lung cancer: a meta-analysis.Drug design, development and therapy · 2015Pooled it
- Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis.PloS one · 2014Pooled it
- The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis.British journal of cancer · 2013Pooled it
- Pooled it
- Role of Histone Modifications and miRNA Regulations in the Toxicity of Trichloroethylene in Terms of Cell Cycle Regulation in Human Kidney Cells.Journal of applied toxicology : JAT · 2026Article
- Association of CDKN2A/B and MTAP deletions in adult-type diffuse gliomas.Journal of neuropathology and experimental neurology · 2026Article
- Article
- Senescence-associated and immune-related 9p21.3 locus genes in colorectal cancer: epigenetic architecture, molecular landscape and therapeutic possibilities.Frontiers in cell and developmental biology · 2026Review
- Molecular Pathways and Biomarkers in Endometrial Carcinoma: Paving the Way for Precision Medicine.Anti-cancer agents in medicinal chemistry · 2026Review
- Taxonomy, carcinogenic mechanisms, and advanced molecular diagnosis of Fusobacterium nucleatum in colorectal cancer: from bench to clinical practice.Frontiers in immunology · 2026Review
- A First-in-Class Chemical-Induced Proximity System Achieves Dose-Dependent Control of Tumor Protein P53 Gene Activation in Preclinical Models of Gastric Cancer.ACS pharmacology & translational science · 2025Article
- Melanoma and Colorectal Cancer as Second Primary Cancers: A Scoping Review of Their Association and the Underlying Biological, Lifestyle, and Genetic Factors.Journal of gastrointestinal cancer · 2025Article
- Insight into the role of DNA methylation in prognosis and treatment response prediction of gastrointestinal cancers.Epigenomics · 2025Review
- Article
- Prognostic alternative mRNA splicing in lung adenocarcinoma.Frontiers in oncology · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
A cyclin-dependent kinase inhibitor CDKN2A (p16/Ink4a) is a tumor suppressor and upregulated in cellular senescence. CDKN2A promoter methylation and gene silencing are associated with the CpG island methylator phenotype (CIMP) in colon cancer. However, prognostic significance of CDKN2A methylation or loss of CDKN2A (p16) expression independent of CIMP status remains uncertain. Using a database of 902 colorectal cancers in 2 independent cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study), we quantified CDKN2A promoter methylation and detected hypermethylation in 269 tumors (30%). By immunohistochemistry, we detected loss of CDKN2A (p16) expression in 25% (200/804) of tumors. We analyzed for LINE-1 hypomethylation and hypermethylation at 7 CIMP-specific CpG islands (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); microsatellite instability (MSI); KRAS, BRAF and PIK3CA mutations; and expression of TP53 (p53), CTNNB1 (β-catenin), CDKN1A (p21), CDKN1B (p27), CCND1 (cyclin D1), FASN (fatty acid synthase) and PTGS2 (cyclooxygenase-2). CDKN2A promoter methylation and loss of CDKN2A (p16) were associated with shorter overall survival in univariate Cox regression analysis [hazard ratio (HR): 1.36, 95% CI: 1.10-1.66, p = 0.0036 for CDKN2A methylation; HR: 1.30, 95% CI: 1.03-1.63, p = 0.026 for CDKN2A (p16) loss] but not in multivariate analysis that adjusted for clinical and tumor variables, including CIMP, MSI and LINE-1 methylation. Neither CDKN2A promoter methylation nor loss of CDKN2A (p16) was associated with colorectal cancer-specific mortality in uni- or multivariate analysis. Despite its well-established role in carcinogenesis, CDKN2A (p16) promoter methylation or loss of expression in colorectal cancer is not independently associated with patient prognosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.