Evidence map›Paper›PMID 38441165›Full record

ArticleMutagenesis2025

Inflammation and gut barrier function-related genes and colorectal cancer risk in western European populations.

Hannah B Mandle, Mazda Jenab, Marc J Gunter, Anne Tjønneland, Anja Olsen, Christina C Dahm, Jie Zhang, Pierre-Emmanuel Sugier, Joseph Rothwell, Gianluca Severi and 21 more

Open access · hybridAbstract read
In one paragraph

Article in Mutagenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

31 authors at 20 institutions in 9 countries.

Hannah B MandleDepartment of Epidemiology, Emory Rollins School of Public Health, Atlanta, GA 30322, USA.ORCID 0000-0002-0277-9607
Mazda JenabNutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
Marc J GunterNutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
Anne TjønnelandDiet, Cancer and Health, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.
Anja OlsenDepartment of Public Health, University of Copenhagen, 1353 Copenhagen K, Denmark.ORCID 0000-0003-4788-503X
Christina C DahmDepartment of Public Health, Aarhus University, DK-8000 Aarhus C, Denmark.
Jie ZhangDepartment of Public Health, Aarhus University, DK-8000 Aarhus C, Denmark.
Pierre-Emmanuel SugierUniversité Paris-Saclay, UVSQ, Inserm 'Exposome and Heredity' team, CESP U1018, 94807 Villejuif Cedex, France.
Joseph RothwellUniversité Paris-Saclay, UVSQ, Inserm 'Exposome and Heredity' team, CESP U1018, 94807 Villejuif Cedex, France.ORCID 0000-0002-6927-3360
Gianluca SeveriUniversité Paris-Saclay, UVSQ, Inserm 'Exposome and Heredity' team, CESP U1018, 94807 Villejuif Cedex, France.
Rudolf KaaksDivision of Cancer Epidemiology, German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany.ORCID 0000-0003-3751-3929
Verena A KatzkeDivision of Cancer Epidemiology, German Cancer Research Center, DKFZ, 69120 Heidelberg, Germany.
Matthias B SchulzeDepartment of Molecular Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, 14469 Nuthetal, Germany.ORCID 0000-0002-0830-5277
Giovanna MasalaInstitute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy.ORCID 0000-0002-5758-9069
Sabina SieriEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy.ORCID 0000-0001-5201-172X
Salvatore PanicoDipartimento Di Medicina Clinica E Chirurgia, Federico II University, 80131 Naples, Italy.
Carlotta SacerdoteUnit of Cancer Epidemiology, AOU Città della Salute e della Scienza University Hospital, 10126 Turin, Italy.ORCID 0000-0002-8008-5096
Catalina BonetUnit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, 0890x Barcelona, Spain.
Maria-Jose SánchezEscuela Andaluza de Salud Pública (EASP), 18011 Granada, Spain.
Pilar AmianoCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.
José María HuertaCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.
Marcela GuevaraCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.ORCID 0000-0001-9242-6364
Richard PalmqvistDepartment of Medical Biosciences, Umea University, 901 87 Umeå, Sweden.
Thyra LöwenmarkDepartment of Medical Biosciences, Umea University, 901 87 Umeå, Sweden.
Aurora Perez-CornagoCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.ORCID 0000-0002-5652-356X
Elisabete WeiderpassOffice of the Director, International Agency for Research on Cancer, 69366 Lyon Cedex 07, France.
Alicia K HeathDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK.
Amanda J CrossDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK.ORCID 0000-0002-0893-2377
Paolo VineisMRC Centre for Environment and Health, School of public Health, Imperial College London, London W2 1PG, UK.ORCID 0000-0001-8935-4566
David J HughesCancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.ORCID 0000-0003-1668-8770
Veronika FedirkoDepartment of Epidemiology, Emory Rollins School of Public Health, Atlanta, GA 30322, USA.ORCID 0000-0002-7805-9913
Centre international de recherche sur le cancer · FRAarhus University · DKGerman Cancer Research Center · DEImperial College London · GBInserm · FRUmeå University · SEUniversity of Copenhagen · DKAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITBasque Government · ESBellvitge University Hospital · ESCentre National de la Recherche Scientifique · FREmory University · USFederico II University Hospital · ITFondazione IRCCS Istituto Nazionale dei Tumori · ITInstituto de Salud Pública de Navarra · ESItalian institute for Genomic Medicine · ITPrevention Institute · USServicio Murciano de Salud · ESThe University of Texas MD Anderson Cancer Center · USUniversidad de Granada · ES

Funding

Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy)Basque Country, Murcia and NavarraCancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award RR200056Cancer Research UK 25004Cancer Research UK PRCRPG-NOV22/100001Catalan Institute of Oncology-ICO (Spain)Danish Cancer Society (Denmark)Department of Epidemiology and BiostatisticsDutch Ministry of Public Health, Welfare and Sports (VWS)Dutch Prevention FundsDutch ZON (Zorg Onderzoek Nederland)Federal Ministry of Education and Research (BMBF) (Germany)German Cancer Aid, German Cancer Research Center (DKFZ)German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)Health Research Board (HRB) of Ireland health research award HRA-POR-2013-397Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII)Institut Gustave RoussyInstitut National de la Santé et de la Recherche Médicale (INSERM) (France)International Agency for Research on Cancer (IARC)Ligue Contre le CancerLK Research FundsMedical Research CouncilMutuelle Générale de l'Education NationaleNetherlands Cancer Registry (NKR)NIHR Imperial Biomedical Research Centre (BRC)Regional Governments of Andalucía, AsturiasSchool of Public Health, Imperial College LondonStatistics Netherlands (The Netherlands)Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden)Wereld Kanker Onderzoek FondsWorld Cancer Research Fund (WCRF)World Cancer Research Fund (WCRF) International Regular Grant Programme 2010-251World Health Organization 001
6 · The paper itself

Abstract

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N = 1374; colon = 871, rectum = 503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set of participants (Ncases = 1001; Ncontrols = 667). Forty-two unique SNPs from 19 different genes were associated with serum biomarkers at Punadjusted ≤ 0.05 among controls. Among SNPs associated with a gut permeability score, 24 SNPs were in genes related to LPS sensing and mucin synthesis. Nine out of 12 SNPs associated with CRP were in genes related to inflammation or Crohn's disease. TLR4 was associated with colon cancer at the SNP level (nine SNPs, all Punadjusted ≤ 0.04) and at the gene level (Punadjusted ≤ 0.01). TLR4 rs10759934 was associated with rectal cancer but not colon cancer. Similarly, IL10 was associated with rectal cancer risk at an SNP and gene level (both Punadjusted ≤ 0.01), but not colon cancer. Genes and SNPs were selected a priori; therefore, we present unadjusted P-values. However, no association was statistically significant after multiple testing correction. This large and comprehensive study has identified gut barrier function and inflammation-related genes possibly contributing to CRC risk in European populations and is consistent with potential etiological links between host genetic background, gut barrier permeability, microbial endotoxemia, and CRC development.

Indexed as

Colorectal NeoplasmsInflammationAdultAgedCase-Control StudiesC-Reactive ProteinEuropeFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedPolymorphism, Single NucleotideProspective StudiesRisk FactorsToll-Like Receptor 4C-Reactive ProteinToll-Like Receptor 4colorectal neoplasmsgut barrierincidenceinflammationsingle nucleotide polymorphism

Identifiers

PMID38441165
PMCPMC11911009
OpenAlexW4392459073

What OpenQuestion holds

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LicenceCC BY-NC
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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.