Evidence map›Paper›PMID 23049789›Full record

ArticlePloS one2012

A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer.

Marina Antelo, Francesc Balaguer, Jinru Shia, Yan Shen, Keun Hur, Leticia Moreira, Miriam Cuatrecasas, Luis Bujanda, Maria Dolores Giraldez, Masanobu Takahashi and 11 more

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 3 pooled it
8.5field-weighted citation impact, top 2% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 3 syntheses or guidelines pooled it, 258 citations in OpenAlex.

  1. Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2024
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86 more citing papers are in PubMed but not listed here.

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

21 authors at 9 institutions in 2 countries.

Marina AnteloOncology and Pathology Sections, Hospital of Gastroenterology "Dr. C. B. Udaondo", Buenos Aires, Argentina.
Francesc Balaguer
Jinru Shia
Yan Shen
Keun Hur
Leticia Moreira
Miriam Cuatrecasas
Luis Bujanda
Maria Dolores Giraldez
Masanobu Takahashi
Ana Cabanne
Mario Edmundo Barugel
Mildred Arnold
Enrique Luis Roca
Montserrat Andreu
Sergi Castellvi-Bel
Xavier Llor
Rodrigo Jover
Antoni Castells
C Richard Boland
Ajay Goel
Baylor University Medical Center · USConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESBiogipuzkoa Health Research Institute · ESHospital Del Mar · ESHospital General Universitario de Alicante Doctor Balmis · ESMemorial Sloan Kettering Cancer Center · USUniversitat de Barcelona · ESUniversity of Illinois Chicago · US

Funding

The Biology and Diagnosis of HNPCCR01CA072851 · NCI · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI GOEL, AJAY · 1996 to 2019
$6.6M
Measuring Methylation Kinetics in Cancer Cells: Computations and ExperimentsR01CA129286 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KOMAROVA, NATALIA L · 2008 to 2012
$1.5M
NCI NIH HHS CA129286NCI NIH HHS R01 CA072851NCI NIH HHS R01 CA129286NCI NIH HHS R01 CA72851
6 · The paper itself

Abstract

objectiveEarly-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously.

designWe analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤ 50 years old (n=188), a group of sporadic CRC >50 years (MSS n=89; MSI n=46), and a group of Lynch syndrome CRCs (n=20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated.

resultsMean LINE-1 methylation levels (± SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥ 65% LINE-1 methylation had significantly better overall survival (p=0.026, log rank test).

conclusionsLINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.

Indexed as

Long Interspersed Nucleotide ElementsAdaptor Proteins, Signal TransducingAdenomaAdultAge of OnsetArgentinaCase-Control StudiesColorectal NeoplasmsColorectal Neoplasms, Hereditary NonpolyposisDNA-Binding ProteinsDNA GlycosylasesDNA MethylationFemaleGene ExpressionGerm-Line MutationHumansAdaptor Proteins, Signal TransducingBRAF protein, humanDNA-Binding ProteinsDNA GlycosylasesMLH1 protein, humanMSH3 protein, humanMutL Protein Homolog 1MutS Homolog 3 ProteinmutY adenine glycosylaseNuclear ProteinsProto-Oncogene Proteins B-raf

Identifiers

PMID23049789
PMCPMC3458035
OpenAlexW2043363016

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.