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@ARTICLE{Mandle:288812,
author = {H. B. Mandle and M. Jenab and M. J. Gunter and A.
Tjønneland and A. Olsen and C. C. Dahm and J. Zhang and
P.-E. Sugier and J. Rothwell and G. Severi and R. Kaaks$^*$
and V. A. Katzke$^*$ and M. B. Schulze and G. Masala and S.
Sieri and S. Panico and C. Sacerdote and C. Bonet and M.-J.
Sánchez and P. Amiano and J. M. Huerta and M. Guevara and
R. Palmqvist and T. Löwenmark and A. Perez-Cornago and E.
Weiderpass and A. K. Heath and A. J. Cross and P. Vineis and
D. J. Hughes and V. Fedirko},
title = {{I}nflammation and {G}ut {B}arrier {F}unction-{R}elated
{G}enes and {C}olorectal {C}ancer {R}isk in {W}estern
{E}uropean {P}opulations.},
journal = {Mutagenesis},
volume = {40},
number = {1},
issn = {0267-8357},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2024-00483},
pages = {48-60},
year = {2025},
note = {2025 Mar 15;40(1):48-60},
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=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.},
keywords = {colorectal neoplasms (Other) / gut barrier (Other) /
incidence (Other) / inflammation (Other) / single nucleotide
polymorphism (SNP) (Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38441165},
doi = {10.1093/mutage/geae008},
url = {https://inrepo02.dkfz.de/record/288812},
}