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@ARTICLE{Beyerle:147669,
author = {J. Beyerle$^*$ and A. N. Holowatyj and M. Haffa$^*$ and E.
Frei$^*$ and B. Gigic and P. Schrotz-King$^*$ and J. Böhm
and N. Habermann and M. Stiborova and D. Scherer and T.
Koelsch and S. Skender$^*$ and N. Becker$^*$ and E. Herpel
and M. Schneider and A. Ulrich and P. Schirmacher and J.
Chang-Claude$^*$ and H. Brenner$^*$ and M. Hoffmeister$^*$
and U. Haug and R. W. Owen$^*$ and C. M. Ulrich},
title = {{E}xpression patterns of xenobiotic metabolizing enzymes in
tumor and adjacent normal mucosa tissues among patients with
colorectal cancer: {T}he {C}olo{C}are {S}tudy.},
journal = {Cancer epidemiology, biomarkers $\&$ prevention},
volume = {29},
number = {2},
issn = {1538-7755},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2019-02658},
pages = {460-469},
year = {2020},
note = {2020 Feb;29(2):460-469#EA:C120#},
abstract = {Xenobiotic metabolizing enzymes (XMEs) play a critical role
in the activation and detoxification of several carcinogens.
However, the role of XMEs in colorectal carcinogenesis is
unclear.We investigated the expression of XMEs in human
colorectal tissues among n=71 stage I-IV colorectal cancer
(CRC) patients from the ColoCare Study. Transcriptomic
profiling using paired colorectal tumor and adjacent normal
mucosa tissues of XMEs
(GSTM1,GSTA1,UGT1A8,UGT1A10,CYP3A4,CYP2C9,GSTP1,CYP2W1) by
RNA microarray was compared using Wilcoxon rank-sum tests.
We assessed associations between clinicopathologic, dietary,
and lifestyle-related factors and XME expression with linear
regression models.GSTM1, GSTA1, UGT1A8, UGT1A10, CYP3A4 were
all statistically significantly downregulated in colorectal
tumor relative to normal mucosa tissues (all p≤0.03).
Women had significantly higher expression of GSTM1 in normal
tissues compared to men (β=0.37,p-value=0.02). By tumor
site, CYP2C9 expression was lower in normal mucosa among
rectal cancer patients versus colon cancer cases
(β=-0.21,p-value=0.0005). Smokers demonstrated higher
CYP2C9 expression levels in normal mucosa (β=0.17,p=0.02)
when compared with non-smokers. Individuals who used NSAIDs
had higher GSTP1 tumor expression compared to non-NSAID
users (β=0.17,p=0.03). Higher consumption of cooked
vegetables (>1x/week) was associated with higher CYP3A4
expression in colorectal tumor tissues
(β=0.14,p=0.007).XMEs have lower expression in colorectal
tumor relative to normal mucosa tissues and may modify
colorectal carcinogenesis via associations with clinical,
lifestyle- and dietary-related factors.Better understanding
into the role of drug-metabolizing enzymes in CRC may reveal
biological differences that contribute to cancer development
as well as treatment response, leading to clinical
implications in CRC prevention and management.},
cin = {C120 / C020 / C070 / HD01},
ddc = {610},
cid = {I:(DE-He78)C120-20160331 / I:(DE-He78)C020-20160331 /
I:(DE-He78)C070-20160331 / I:(DE-He78)HD01-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31740522},
doi = {10.1158/1055-9965.EPI-19-0449},
url = {https://inrepo02.dkfz.de/record/147669},
}