Inflammation and Gut Barrier Function-Related Genes and Colorectal Cancer Risk in Western European Populations
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Inflammation and Gut Barrier Function-Related Genes and Colorectal Cancer Risk in Western European Populations. / Mandle, Hannah B; Jenab, Mazda; Gunter, Marc J; Tjønneland, Anne; Olsen, Anja; Dahm, Christina C; Zhang, Jie; Sugier, Pierre-Emmanuel; Rothwell, Joseph; Severi, Gianluca; Kaaks, Rudolf; Katzke, Verena A; Schulze, Matthias B; Masala, Giovanna; Sieri, Sabina; Panico, Salvatore; Sacerdote, Carlotta; Bonet, Catalina; Sánchez, Maria-Jose; Amiano, Pilar; Huerta, José María; Guevara, Marcela; Palmqvist, Richard; Löwenmark, Thyra; Perez-Cornago, Aurora; Weiderpass, Elisabete; Heath, Alicia K; Cross, Amanda J; Vineis, Paolo; Hughes, David J; Fedirko, Veronika.
I: Mutagenesis, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Inflammation and Gut Barrier Function-Related Genes and Colorectal Cancer Risk in Western European Populations
AU - Mandle, Hannah B
AU - Jenab, Mazda
AU - Gunter, Marc J
AU - Tjønneland, Anne
AU - Olsen, Anja
AU - Dahm, Christina C
AU - Zhang, Jie
AU - Sugier, Pierre-Emmanuel
AU - Rothwell, Joseph
AU - Severi, Gianluca
AU - Kaaks, Rudolf
AU - Katzke, Verena A
AU - Schulze, Matthias B
AU - Masala, Giovanna
AU - Sieri, Sabina
AU - Panico, Salvatore
AU - Sacerdote, Carlotta
AU - Bonet, Catalina
AU - Sánchez, Maria-Jose
AU - Amiano, Pilar
AU - Huerta, José María
AU - Guevara, Marcela
AU - Palmqvist, Richard
AU - Löwenmark, Thyra
AU - Perez-Cornago, Aurora
AU - Weiderpass, Elisabete
AU - Heath, Alicia K
AU - Cross, Amanda J
AU - Vineis, Paolo
AU - Hughes, David J
AU - Fedirko, Veronika
N1 - © The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2024
Y1 - 2024
N2 - 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=1,374; 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=1,001; 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 a 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.
AB - 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=1,374; 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=1,001; 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 a 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.
U2 - 10.1093/mutage/geae008
DO - 10.1093/mutage/geae008
M3 - Journal article
C2 - 38441165
JO - Mutagenesis
JF - Mutagenesis
SN - 0267-8357
ER -
ID: 390290573