Evidence map›Paper›PMID 26451011›Full record

SynthesisInternational journal of epidemiology2016

Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas.

Zahra Montazeri, Evropi Theodoratou, Christine Nyiraneza, Maria Timofeeva, Wanjing Chen, Victoria Svinti, Shanya Sivakumaran, Gillian Gresham, Laura Cubitt, Luis Carvajal-Carmona and 7 more

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in International journal of epidemiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 4 pooled it
2.0field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 4 syntheses or guidelines pooled it, 25 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. Journal of clinical medicine · 2023
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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

17 authors at 7 institutions in 3 countries.

Zahra MontazeriSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada.
Evropi TheodoratouCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Christine NyiranezaSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada.
Maria TimofeevaColon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK.
Wanjing ChenCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Victoria SvintiColon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK.
Shanya SivakumaranCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Gillian GreshamSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada.
Laura CubittCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Luis Carvajal-CarmonaBiochemistry and Molecular Medicine, Genome and Biomedical Sciences Facility, UC Davis School of Medicine, University of California Davis, Davis, CA, USA.
Monica M BertagnolliDepartment of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Ann G ZauberDepartment of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA and.
Ian TomlinsonWellcome Trust Centre for Human Genetics, Oxford, UK.
Susan M FarringtonColon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK.
Malcolm G DunlopColon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK.
Harry CampbellCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK, Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK.
Julian LittleSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada, jlittle@uottawa.ca.
University of Edinburgh · GBUniversity of Ottawa · CAWestern General Hospital · GBMRC Institute of Genetics and Molecular Medicine · GBBrigham and Women's Hospital · USCentre for Human Genetics · GBMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Cancer Research UK 12076Cancer Research UK 16459Cancer Research UK 18927Medical Research Council MC_PC_U127527198Medical Research Council MC_U127527198Medical Research Council MR/K018647/1NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundLow penetrance genetic variants, primarily single nucleotide polymorphisms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here we report the first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database [http://www.chs.med.ed.ac.uk/CRAgene/].

methodsWe performed a systematic review, reviewing 9750 titles, and then extracted data from 130 publications reporting on 181 polymorphisms in 74 genes. We conducted meta-analyses to derive summary effect estimates for 37 polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False Discovery Probability (BFDP) to assess the levels of the credibility of associations.

resultsWe considered the association with the rs6983267 variant at 8q24 as 'highly credible', reaching genome-wide statistical significance in at least one meta-analysis model. We identified 'less credible' associations (higher heterogeneity, lower statistical power, BFDP > 0.02) with a further four variants of four independent genes: MTHFR c.677C>T p.A222V (rs1801133), TP53 c.215C>G p.R72P (rs1042522), NQO1 c.559C>T p.P187S (rs1800566), and NAT1 alleles imputed as fast acetylator genotypes. For the remaining 32 variants of 22 genes for which positive associations with CRA risk have been previously reported, the meta-analyses revealed no credible evidence to support these as true associations.

conclusionsThe limited number of credible associations between low penetrance genetic variants and CRA reflects the lower volume of evidence and associated lack of statistical power to detect associations of the magnitude typically observed for genetic variants and chronic diseases. The CRA gene database provides context for CRA genetic association data and will help inform future research directions.

Indexed as

Polymorphism, Single NucleotideAdenomaAllelesArylamine N-AcetyltransferaseBayes TheoremColorectal NeoplasmsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIsoenzymesMethylenetetrahydrofolate Reductase (NADPH2)NAD(P)H Dehydrogenase (Quinone)Risk FactorsTumor Suppressor Protein p53Arylamine N-AcetyltransferaseIsoenzymesMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanN-acetyltransferase 1NAD(P)H Dehydrogenase (Quinone)NQO1 protein, humanTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID26451011
PMCPMC5860727
OpenAlexW1708123936

What OpenQuestion holds

Textmetadata
LicenceTDM
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.