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000147669 1001_ $$0P:(DE-He78)a286621712d6d390c909e519145368d0$$aBeyerle, Jolantha$$b0$$eFirst author
000147669 245__ $$aExpression patterns of xenobiotic metabolizing enzymes in tumor and adjacent normal mucosa tissues among patients with colorectal cancer: The ColoCare Study.
000147669 260__ $$aPhiladelphia, Pa.$$bAACR$$c2020
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000147669 520__ $$aXenobiotic metabolizing enzymes (XMEs) play a critical role in the activation and detoxification of several carcinogens. However, the role of XMEs in colorectal carcinogenesis is unclear.We investigated the expression of XMEs in human colorectal tissues among n=71 stage I-IV colorectal cancer (CRC) patients from the ColoCare Study. Transcriptomic profiling using paired colorectal tumor and adjacent normal mucosa tissues of XMEs (GSTM1,GSTA1,UGT1A8,UGT1A10,CYP3A4,CYP2C9,GSTP1,CYP2W1) by RNA microarray was compared using Wilcoxon rank-sum tests. We assessed associations between clinicopathologic, dietary, and lifestyle-related factors and XME expression with linear regression models.GSTM1, GSTA1, UGT1A8, UGT1A10, CYP3A4 were all statistically significantly downregulated in colorectal tumor relative to normal mucosa tissues (all p≤0.03). Women had significantly higher expression of GSTM1 in normal tissues compared to men (β=0.37,p-value=0.02). By tumor site, CYP2C9 expression was lower in normal mucosa among rectal cancer patients versus colon cancer cases (β=-0.21,p-value=0.0005). Smokers demonstrated higher CYP2C9 expression levels in normal mucosa (β=0.17,p=0.02) when compared with non-smokers. Individuals who used NSAIDs had higher GSTP1 tumor expression compared to non-NSAID users (β=0.17,p=0.03). Higher consumption of cooked vegetables (>1x/week) was associated with higher CYP3A4 expression in colorectal tumor tissues (β=0.14,p=0.007).XMEs have lower expression in colorectal tumor relative to normal mucosa tissues and may modify colorectal carcinogenesis via associations with clinical, lifestyle- and dietary-related factors.Better understanding into the role of drug-metabolizing enzymes in CRC may reveal biological differences that contribute to cancer development as well as treatment response, leading to clinical implications in CRC prevention and management.
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000147669 7001_ $$00000-0001-8001-8793$$aHolowatyj, Andreana N$$b1
000147669 7001_ $$0P:(DE-He78)131e5921fcfccbf0f978d4426f1a615b$$aHaffa, Mariam$$b2$$udkfz
000147669 7001_ $$0P:(DE-HGF)0$$aFrei, Eva$$b3
000147669 7001_ $$aGigic, Biljana$$b4
000147669 7001_ $$0P:(DE-He78)01ef71f71b01a3ec3b698653fd43fe86$$aSchrotz-King, Petra$$b5$$udkfz
000147669 7001_ $$aBöhm, Jürgen$$b6
000147669 7001_ $$aHabermann, Nina$$b7
000147669 7001_ $$00000-0001-5430-4403$$aStiborova, Marie$$b8
000147669 7001_ $$aScherer, Dominique$$b9
000147669 7001_ $$aKoelsch, Torsten$$b10
000147669 7001_ $$0P:(DE-HGF)0$$aSkender, Stephanie$$b11
000147669 7001_ $$0P:(DE-He78)1573258b58c33f1922ca9719d0c8c4ab$$aBecker, Nikolaus$$b12$$udkfz
000147669 7001_ $$aHerpel, Esther$$b13
000147669 7001_ $$aSchneider, Martin$$b14
000147669 7001_ $$aUlrich, Alexis$$b15
000147669 7001_ $$aSchirmacher, Peter$$b16
000147669 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b17$$udkfz
000147669 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b18$$udkfz
000147669 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b19$$udkfz
000147669 7001_ $$aHaug, Ulrike$$b20
000147669 7001_ $$0P:(DE-He78)43996fb100428b0d99e233c3261f7187$$aOwen, Robert W$$b21$$udkfz
000147669 7001_ $$aUlrich, Cornelia M$$b22
000147669 773__ $$0PERI:(DE-600)2036781-8$$a10.1158/1055-9965.EPI-19-0449$$gp. cebp.0449.2019 -$$n2$$p460-469$$tCancer epidemiology, biomarkers & prevention$$v29$$x1538-7755$$y2020
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