TY  - JOUR
AU  - Beyerle, Jolantha
AU  - Holowatyj, Andreana N
AU  - Haffa, Mariam
AU  - Frei, Eva
AU  - Gigic, Biljana
AU  - Schrotz-King, Petra
AU  - Böhm, Jürgen
AU  - Habermann, Nina
AU  - Stiborova, Marie
AU  - Scherer, Dominique
AU  - Koelsch, Torsten
AU  - Skender, Stephanie
AU  - Becker, Nikolaus
AU  - Herpel, Esther
AU  - Schneider, Martin
AU  - Ulrich, Alexis
AU  - Schirmacher, Peter
AU  - Chang-Claude, Jenny
AU  - Brenner, Hermann
AU  - Hoffmeister, Michael
AU  - Haug, Ulrike
AU  - Owen, Robert W
AU  - Ulrich, Cornelia M
TI  - Expression patterns of xenobiotic metabolizing enzymes in tumor and adjacent normal mucosa tissues among patients with colorectal cancer: The ColoCare Study.
JO  - Cancer epidemiology, biomarkers & prevention
VL  - 29
IS  - 2
SN  - 1538-7755
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2019-02658
SP  - 460-469
PY  - 2020
N1  - 2020 Feb;29(2):460-469#EA:C120#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31740522
DO  - DOI:10.1158/1055-9965.EPI-19-0449
UR  - https://inrepo02.dkfz.de/record/147669
ER  -