ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
The A/G allele of rs16906252 predicts for MGMT methylation and is selectively silenced in premalignant lesions from smokers and in lung adenocarcinomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Efficiency for evaluation of disease etiologic heterogeneity in case-case and case-control studies.The international journal of biostatistics · 2025Article
- Genetic Ancestry and Lung Cancer in Latin American Patients: A Crucial Step for Understanding a Diverse Population.Clinical lung cancer · 2025Review
- Constitutional Epimutations: From Rare Events Toward Major Cancer Risk Factors?JCO precision oncology · 2025Review
- MGMT epimutations and risk of incident cancer of the colon, glioblastoma multiforme, and diffuse large B cell lymphomas.Clinical epigenetics · 2025Article
- IncreasedMolecular & cellular oncology · 2025Article
- Single nucleotide variants in lung cancer.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Discrimination between 34 of 36 Possible Combinations of Three C>T SNP Genotypes in theInternational journal of molecular sciences · 2021Article
- Constitutional Mosaic Epimutations - a hidden cause of cancer?Cell stress · 2019Review
- Dietary Nutrient Intake, Ethnicity, and Epigenetic Silencing of Lung Cancer Genes Detected in Sputum in New Mexican Smokers.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- The rs16906252:C>T SNP is not associated with increased overall survival or temozolomide response in a Han-Chinese glioma cohort.PloS one · 2017Article
- The MGMT promoter single-nucleotide polymorphism rs1625649 had prognostic impact on patients with MGMT methylated glioblastoma.PloS one · 2017Article
- SNP rs16906252C>T Is an Expression and Methylation Quantitative Trait Locus Associated with an Increased Risk of Developing MGMT-Methylated Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Assessment of Quantitative and Allelic MGMT Methylation Patterns as a Prognostic Marker in Glioblastoma.Journal of neuropathology and experimental neurology · 2016Article
- Statistical methods for studying disease subtype heterogeneity.Statistics in medicine · 2016Article
- Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas.Clinical epigenetics · 2016Article
- The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide.Neuro-oncology · 2015Article
- A Meta-Regression Method for Studying Etiological Heterogeneity Across Disease Subtypes Classified by Multiple Biomarkers.American journal of epidemiology · 2015Article
- Implication of a Chromosome 15q15.2 Locus in Regulating UBR1 and Predisposing Smokers to MGMT Methylation in Lung.Cancer research · 2015Article
- Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
purposeTo address the association between sequence variants within the MGMT (O(6)-methylguanine-DNA methyltransferase) promoter-enhancer region and methylation of MGMT in premalignant lesions from smokers and lung adenocarcinomas, their biological effects on gene regulation, and targeting MGMT for therapy. EXPERIMENTAL
designSingle nucleotide polymorphisms (SNP) identified through sequencing a 1.9 kb fragment 5' of MGMT were examined in relation to MGMT methylation in 169 lung adenocarcinomas and 1,731 sputum samples from smokers. The effect of promoter haplotypes on MGMT expression was tested using a luciferase reporter assay and cDNA expression analysis along with allele-specific sequencing for methylation. The response of MGMT methylated lung cancer cell lines to the alkylating agent temozolomide (TMZ) was assessed.
resultsThe A allele of rs16906252 and the haplotype containing this SNP were strongly associated with increased risk for MGMT methylation in adenocarcinomas (ORs ≥ 94). This association was observed to a lesser extent in sputum samples in both smoker cohorts. The A allele was selectively methylated in primary lung tumors and cell lines heterozygous for rs16906252. With the most common haplotype as the reference, a 20 to 41% reduction in promoter activity was seen for the haplotype carrying the A allele that correlated with lower MGMT expression. The sensitivity of lung cancer cell lines to TMZ was strongly correlated with levels of MGMT methylation and expression.
conclusionsThese studies provide strong evidence that the A allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in lung carcinogenesis. Moreover, TMZ treatment may benefit a subset of lung cancer patients methylated for MGMT.
Indexed as
Identifiers
What OpenQuestion holds
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.