Evidence map›Paper›PMID 25996601›Full record

ArticlePloS one2015

Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer.

Yasushi Hamaya, Carla Guarinos, Stephanie S Tseng-Rogenski, Moriya Iwaizumi, Ritabrata Das, Rodrigo Jover, Antoni Castells, Xavier Llor, Montserrat Andreu, John M Carethers

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 38 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. THE JEREMIAH METZGER LECTURE: ENVIRONMENTAL INFLUENCES ON COLORECTAL CANCER.Transactions of the American Clinical and Climatological Association · 2024
    Article
  5. High expression ofThe Indian journal of medical research · 2022
    Article
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  15. Review
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  17. Article
  18. Risk factors for colon location of cancer.Translational gastroenterology and hepatology · 2018
    Article
  19. Review
  20. Review
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 6 institutions in 2 countries.

Yasushi HamayaDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Carla GuarinosDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America; Unidad de Gastroenterologia, Hospital General Universitario de Alicante, Alicante, Spain.
Stephanie S Tseng-RogenskiDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Moriya IwaizumiDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Ritabrata DasBiostatistics Department, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
Rodrigo JoverUnidad de Gastroenterologia, Hospital General Universitario de Alicante, Alicante, Spain.
Antoni CastellsDepartment of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Spain.
Xavier LlorDivision of Gastroenterology, Department of Medicine, Yale University, New Haven, Connecticut, United States of America.
Montserrat AndreuDepartment of Gastroenterology, Hospital del Mar, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Pompeu Fabra University, Barcelona, Catalonia, Spain.
John M CarethersDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
University of Michigan–Ann Arbor · USHospital General Universitario de Alicante Doctor Balmis · ESMichigan United · USPompeu Fabra University · ESUniversitat de Barcelona · ESYale University · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
MICROSATELLITE INSTABILITY &DNA MISMATCH REPAIR SYSTEMR01DK067287 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CARETHERS, JOHN M · 2005 to 2015
$3.2M
Inflammatory Differentiation of Colorectal Cancer Among African AmericansU01CA162147 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CARETHERS, JOHN M · 2012 to 2016
$1.4M
NCI NIH HHS CA162147NCI NIH HHS U01 CA162147NIDDK NIH HHS DK067287NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK067287
6 · The paper itself

Abstract

Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective) had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H).

Indexed as

Microsatellite RepeatsAdultAgedAged, 80 and overAntimetabolites, AntineoplasticChemotherapy, AdjuvantColorectal NeoplasmsFemaleFluorouracilHumansKaplan-Meier EstimateMaleMiddle AgedNeoplasm StagingRisk FactorsTreatment OutcomeAntimetabolites, AntineoplasticFluorouracil

Identifiers

PMID25996601
PMCPMC4440728
OpenAlexW2118722885

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.