Evidence map›Paper›PMID 30852420›Full record

SynthesisEuropean journal of cancer (Oxford, England : 1990)2019

Impact of polymorphisms within genes involved in regulating DNA methylation in patients with metastatic colorectal cancer enrolled in three independent, randomised, open-label clinical trials: a meta-analysis from TRIBE, MAVERICC and FIRE-3.

Alberto Puccini, Fotios Loupakis, Sebastian Stintzing, Shu Cao, Francesca Battaglin, Ryuma Togunaka, Madiha Naseem, Martin D Berger, Shivani Soni, Wu Zhang and 10 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European journal of cancer (Oxford, England : 1990), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Medicina (Kaunas, Lithuania) · 2024
    Article
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  3. Review
  4. Article
  5. 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

20 authors at 4 institutions in 3 countries.

Alberto PucciniDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Fotios LoupakisClinical and Experimental Oncology Department, Medical Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Sebastian StintzingComprehensive Cancer Center, Ludwig-Maximilian-University of Munich, Munich, Germany.
Shu CaoDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Francesca BattaglinDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Clinical and Experimental Oncology Department, Medical Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Ryuma TogunakaDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Madiha NaseemDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Martin D BergerDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Shivani SoniDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Wu ZhangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Christoph MancaoOncology Biomarker Development, Genentech Inc., Basel, Switzerland.
Bodour SalhiaDepartment of Translational Genomics, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Shannon M MumenthalerLawrence J. Ellison Institute for Transformative Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Daniel J WeisenbergerDepartment of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Gangning LiangDepartment of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Chiara CremoliniDepartment of Medical Oncology, University of Pisa, Pisa, Italy.
Volker HeinemannComprehensive Cancer Center, Ludwig-Maximilian-University of Munich, Munich, Germany.
Alfredo FalconeDepartment of Medical Oncology, University of Pisa, Pisa, Italy.
Joshua MillsteinDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA. Electronic address: lenz@med.usc.edu.
University of Southern California · USLudwig-Maximilians-Universität München · DEUniversity of Pisa · ITIstituto Oncologico Veneto · IT

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

backgroundCpG island DNA hypermethylation and global DNA hypomethylation are hallmark characteristics of colorectal cancer (CRC). Therefore, we aim to explore the effect of genetic variations within the genes that regulate the DNA methylation and demethylation pathways on outcomes in patients with metastatic CRC (mCRC) treated with first-line therapy and enrolled in three independent, randomised, open-label clinical trials.

methodsA total of 884 patients with mCRC enrolled in TRIBE, MAVERICC and FIRE-3 trials were included. Single-nucleotide polymorphisms (SNPs) within genes involved in DNA methylation and demethylation pathways were analysed. The prognostic value of each SNP across all treatment arms was quantified using the inverse-variance-weighted effect size, a meta-analysis approach implemented in the METASOFT software.

resultsIn the meta-analysis, DNMT3A rs11681717 was significantly associated with overall survival (hazard ratio = 1.26; 95% confidence interval [CI] 1.08-1.46; P = 0.002; false discovery rate [FDR] = 0.016), accounting for seven tests in the DNA methylation pathway. In addition, there was suggestive evidence of association for ten-eleven translocation (TET) genes variance with tumour response (TET1 rs3814177, odds ratio [OR] = 0.76, 95% CI 0.59-0.97, P = 0.025, FDR = 0.087; TET3 rs7560668, OR = 1.44; 95% CI 1.10-1.89; P = 0.009; FDR = 0.062).

conclusionsWe showed that polymorphisms within the genes responsible for the DNA methylation and demethylation machineries are correlated with outcomes in patients with mCRC who were enrolled in three independent, randomised, open-label, phase II/III clinical trials. In addition, we demonstrated the feasibility of a meta-analysis approach to identify stronger and more convincing association between gene polymorphisms and outcome, potentially leading the way to a new method of analysis for similar data set.

Indexed as

AdultAgedColorectal NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AFemaleHumansMaleMiddle AgedPolymorphism, Single NucleotidePrognosisRandomized Controlled Trials as TopicDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanClinical trialsColorectal cancerDNA methylationMeta-analysisSingle-nucleotide polymorphism

Identifiers

PMID30852420
PMCPMC6436973
OpenAlexW2921458196

What OpenQuestion holds

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Registered trials

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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.