Evidence map›Paper›PMID 21140203›Full record

ArticleCancer causes & control : CCC2011

MGMT promoter methylation, loss of expression and prognosis in 855 colorectal cancers.

Kaori Shima, Teppei Morikawa, Yoshifumi Baba, Katsuhiko Nosho, Maiko Suzuki, Mai Yamauchi, Marika Hayashi, Edward Giovannucci, Charles S Fuchs, Shuji Ogino

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer causes & control : CCC, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03832621 (NIVOLUMAB Plus IPILIMUMAB and TEMOZOLOMIDE in Combination in Microsatellite Stable), which is not on this map. Cited by 45 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 7 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

NCT03832621 phase2completednot on this mapstarted 2019, after this paper: background citation

NIVOLUMAB Plus IPILIMUMAB and TEMOZOLOMIDE in Combination in Microsatellite Stable (MSS), MGMT Silenced Metastatic Colorectal Cancer (mCRC): the MAYA Study

TypeinterventionalSponsorFondazione IRCCS Istituto Nazionale dei Tumori, MilanoRan2019 to 2021Enrolled135ConditionsMetastatic Colorectal CancerArmsTemozolomide, Nivolumab, Ipilimumab
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 7 syntheses or guidelines pooled it, 75 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Clinicopathological significance and potential drug target of O6-methylguanine-DNA methyltransferase in colorectal cancer: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Pooled it
  5. Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Pooled it
  6. Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Pooled it
  7. Pooled it
  8. Trial
  9. Germline Predisposition to Oncogenic Alkylating Damage in Colorectal Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
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  11. Review
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  14. Downregulation of MGMT promotes proliferation of intrahepatic cholangiocarcinoma by regulating p21.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020
    Article
  15. Article
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  20. Mapping clinicopathological entities within colorectal mucinous adenocarcinomas: a hierarchical clustering approach.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Kaori ShimaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Teppei Morikawa
Yoshifumi Baba
Katsuhiko Nosho
Maiko Suzuki
Mai Yamauchi
Marika Hayashi
Edward Giovannucci
Charles S Fuchs
Shuji Ogino
Dana-Farber Cancer Institute · USHarvard University · USBrigham and Women's Hospital · US

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI TWOROGER, SHELLEY S · 2000 to 2019
$77.8M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI GIOVANNUCCI, EDWARD · 1991 to 2009
$41.8M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
Epigenetic Events and Colorectal Cancer EpidemiologyR01CA151993 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2010 to 2014
$2.6M
Molecular Epidemiology of Colorectal CancerK07CA122826 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2007 to 2010
$634k
NCI NIH HHS K07 CA122826NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P01 CA55075NCI NIH HHS P01 CA87969NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA151993
6 · The paper itself

Abstract

objectiveO⁶-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme. MGMT promoter hypermethylation and epigenetic silencing often occur as early events in carcinogenesis. However, prognostic significance of MGMT alterations in colorectal cancer remains uncertain.

methodsUtilizing a database of 855 colon and rectal cancers in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study), we detected MGMT promoter hypermethylation in 325 tumors (38%) by MethyLight and loss of MGMT expression in 37% (247/672) of tumors by immunohistochemistry. We assessed the CpG island methylator phenotype (CIMP) using eight methylation markers [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1], and LINE-1 (L1) hypomethylation, TP53 (p53), and microsatellite instability (MSI).

resultsMGMT hypermethylation was not associated with colorectal cancer-specific mortality in univariate or multivariate Cox regression analysis [adjusted hazard ratio (HR) = 1.03; 95% confidence interval (CI), 0.79-1.36] that adjusted for clinical and tumor features, including CIMP, MSI, and BRAF mutation. Similarly, MGMT loss was not associated with patient survival. MGMT loss was associated with G>A mutations in KRAS (p = 0.019) and PIK3CA (p = 0.0031).

conclusionsDespite a well-established role of MGMT aberrations in carcinogenesis, neither MGMT promoter methylation nor MGMT loss serves as a prognostic biomarker in colorectal cancer.

Indexed as

Promoter Regions, GeneticAgedBiomarkers, TumorCarcinomaClass I Phosphatidylinositol 3-KinasesCohort StudiesColorectal NeoplasmsDNA MethylationDNA Modification MethylasesDNA Repair EnzymesFemaleGene Expression Regulation, NeoplasticGene SilencingHumansMaleMiddle AgedBiomarkers, TumorClass I Phosphatidylinositol 3-KinasesDNA Modification MethylasesDNA Repair EnzymesKRAS protein, humanMGMT protein, humanPhosphatidylinositol 3-KinasesPIK3CA protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)ras ProteinsTumor Suppressor Proteins

Identifiers

PMID21140203
PMCPMC3278857
OpenAlexW1989969436

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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.