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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\u2019s disease with colon and rectal cancer risks. Incident CRC cases (N\u2005=\u20051374; colon\u2005=\u2005871, rectum\u2005=\u2005503) 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\u2005=\u20051001; Ncontrols\u2005=\u2005667). Forty-two unique SNPs from 19 different genes were associated with serum biomarkers at Punadjusted\u2005\u2264\u20050.05 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\u2019s disease. TLR4 was associated with colon cancer at the SNP level (nine SNPs, all Punadjusted\u2005\u2264\u20050.04) and at the gene level (Punadjusted\u2005\u2264\u20050.01). 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 \u2264 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.<\/jats:p>","DOI":"10.1093\/mutage\/geae008","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T12:48:50Z","timestamp":1709642930000},"page":"48-60","source":"Crossref","is-referenced-by-count":13,"title":["Inflammation and gut barrier function-related genes and colorectal cancer risk in western European populations"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0277-9607","authenticated-orcid":false,"given":"Hannah B","family":"Mandle","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Emory Rollins School of Public Health , Atlanta, GA 30322 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Copenhagen K ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-503X","authenticated-orcid":false,"given":"Anja","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Copenhagen , 1353 Copenhagen K ,","place":["Denmark"]},{"name":"Department of Public Health, Aarhus University , DK-8000 Aarhus C ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina C","family":"Dahm","sequence":"additional","affiliation":[{"name":"Department of Public Health, Aarhus University , DK-8000 Aarhus C ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Public Health, Aarhus University , DK-8000 Aarhus C ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Emmanuel","family":"Sugier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, Inserm \u2018Exposome and Heredity\u2019 team, CESP U1018 , 94807 Villejuif Cedex ,","place":["France"]},{"name":"Laboratoire de Math\u00e9matiques et de leurs Applications de Pau E2S UPPA, CNRS , 64013 Pau Cedex ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-3360","authenticated-orcid":false,"given":"Joseph","family":"Rothwell","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, Inserm \u2018Exposome and Heredity\u2019 team, CESP U1018 , 94807 Villejuif Cedex ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Severi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, UVSQ, Inserm \u2018Exposome and Heredity\u2019 team, CESP U1018 , 94807 Villejuif Cedex ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3751-3929","authenticated-orcid":false,"given":"Rudolf","family":"Kaaks","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center, DKFZ , 69120 Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena A","family":"Katzke","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center, DKFZ , 69120 Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0830-5277","authenticated-orcid":false,"given":"Matthias B","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology, German Institute of Human Nutrition , Potsdam-Rehbruecke, 14469 Nuthetal ,","place":["Germany"]},{"name":"Institute of Nutritional Science, University of Potsdam , 14469 Nuthetal ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-9069","authenticated-orcid":false,"given":"Giovanna","family":"Masala","sequence":"additional","affiliation":[{"name":"Institute for Cancer Research, Prevention and Clinical Network (ISPRO) , 50139 Florence ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5201-172X","authenticated-orcid":false,"given":"Sabina","family":"Sieri","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano , 20133 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Panico","sequence":"additional","affiliation":[{"name":"Dipartimento Di Medicina Clinica E Chirurgia, Federico II University , 80131 Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-5096","authenticated-orcid":false,"given":"Carlotta","family":"Sacerdote","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, AOU Citt\u00e0 della Salute e della Scienza University Hospital , 10126 Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Bonet","sequence":"additional","affiliation":[{"name":"Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO) , L\u2019Hospitalet de Llobregat, 0890x Barcelona ,","place":["Spain"]},{"name":"Bellvitge Biomedical Research Institute (IDIBELL) , L\u2019Hospitalet de Llobregat, 0890x Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Jose","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Escuela 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,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Palmqvist","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Umea University , 901 87 Ume\u00e5 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thyra","family":"L\u00f6wenmark","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Umea University , 901 87 Ume\u00e5 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-356X","authenticated-orcid":false,"given":"Aurora","family":"Perez-Cornago","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford , Oxford OX3 7LF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabete","family":"Weiderpass","sequence":"additional","affiliation":[{"name":"Office of the 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Imperial College London , London W2 1PG ,","place":["UK"]},{"name":"Italian Institute for Genomic Medicine (IIGM) , 10060 Candiolo TO,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1668-8770","authenticated-orcid":false,"given":"David J","family":"Hughes","sequence":"additional","affiliation":[{"name":"Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin , Dublin 4 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7805-9913","authenticated-orcid":false,"given":"Veronika","family":"Fedirko","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Emory Rollins School of Public Health , Atlanta, GA 30322 ,","place":["USA"]},{"name":"Department of Epidemiology, University of Texas M. 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