Evidence map›Paper›PMID 22875147›Full record

ArticleJournal of human genetics2012

Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer.

Jérémie H Lefevre, Carolina Bonilla, Chrystelle Colas, Bruce Winney, Elaine Johnstone, Susan Tonks, Tammy Day, Katarzyna Hutnik, Abdelhamid Boumertit, Florent Soubrier and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 23% 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, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. The role of heredity in pterygium development.International journal of ophthalmology · 2014
    Review
  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

14 authors at 6 institutions in 2 countries.

Jérémie H Lefevre *Department of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
Carolina Bonilla *Department of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
Chrystelle ColasDepartment of Digestive Surgery, Hôpital Saint-Antoine AP-HP, University Paris VI (Pierre and Marie Curie), Paris, France.
Bruce WinneyDepartment of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
Elaine JohnstoneDepartment of Clinical Pharmacology, Translational Oncology Group, Oxford, UK.
Susan TonksDepartment of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
Tammy DayDepartment of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
Katarzyna HutnikDepartment of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
Abdelhamid BoumertitDepartment of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
Florent SoubrierLaboratory of Angiogenetics and Oncogenetics, Hôpital Pitié-Salpétrière AP-HP, University Paris VI (Pierre and Marie Curie), Paris, France.
Rachel MidgleyDepartment of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
David KerrNuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Yann ParcDepartment of Digestive Surgery, Hôpital Saint-Antoine AP-HP, University Paris VI (Pierre and Marie Curie), Paris, France.
Walter F BodmerDepartment of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK.
University of Oxford · GBAssistance Publique – Hôpitaux de Paris · FRSorbonne Université · FRJohn Radcliffe Hospital · GBOxford Research Group · GBUniversity of Bristol · GB

Funding

Cancer Research UKWellcome Trust 088262
6 · The paper itself

Abstract

Some 15-20% of multiple adenomatous polyposis have no genetic explanation and 20-30% of colorectal cancer (CRC) cases are thought to be due to inherited multifactorial causes. Accumulation of deleterious effects of low-frequency dominant and independently acting variants may be a partial explanation for such patients. The aim of this study was to type a selection of rare and low-frequency variants (<5%) to elucidate their role in CRC susceptibility. A total of 1181 subjects were included (866 controls; 315 cases). Cases comprised UK (n=184) and French (n=131) patients with MAP (n=187) or early-onset CRC (n=128). Seventy variants in 17 genes were examined in cases and controls. The effect of the variant effect on protein function was investigated in silico. Out of the 70 variants typed, 36 (51%) were tested for association. Twenty-one variants were rare (minor allele frequency (MAF) <1%). Four rare variants were found to have a significantly higher MAF in cases (EXO1-12, MLH1-1, CTNNB1-1 and BRCA2-37, P<0.05) than in controls. Pooling all rare variants with a MAF <0.5% showed an excess risk in cases (odds ratio=3.2; 95% confidence interval=1.1-9.5; P=0.04). Rare variants are important risk factors in CRC and, as such, should be systematically assayed alongside common variation in the search for the genetic basis of complex diseases.

Indexed as

Genetic Predisposition to DiseaseGenetic VariationAdaptor Proteins, Signal TransducingAdenomaAdenomatous Polyposis ColiAdultAge of Onsetbeta CateninBRCA2 ProteinCase-Control StudiesColorectal NeoplasmsComputer SimulationDNA Repair EnzymesExodeoxyribonucleasesFranceGene FrequencyAdaptor Proteins, Signal Transducingbeta CateninBRCA2 ProteinBRCA2 protein, humanCTNNB1 protein, humanDNA Repair EnzymesEXO1 protein, humanExodeoxyribonucleasesMLH1 protein, humanMutL Protein Homolog 1Nuclear Proteins

Identifiers

PMID22875147
PMCPMC5140019
OpenAlexW2070116573

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.