Expression Patterns of Xenobiotic-Metabolizing Enzymes in Tumor and Adjacent Normal Mucosa Tissues among Patients with Colorectal Cancer: The ColoCare Study.

Autor:	Beyerle J; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Holowatyj AN; Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.; Huntsman Cancer Institute, Salt Lake City, Utah., Haffa M; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Frei E; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Gigic B; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany., Schrotz-King P; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Boehm J; Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.; Huntsman Cancer Institute, Salt Lake City, Utah., Habermann N; European Molecular Biology Laboratory (EMBL), Heidelberg, Germany., Stiborova M; Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic., Scherer D; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany., Kölsch T; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany., Skender S; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Becker N; NCT Cancer Registry, German Cancer Research Center (DKFZ), Heidelberg, Germany., Herpel E; Institute of Pathology, University Hospital, Heidelberg, Germany.; Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Germany., Schneider M; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany., Ulrich A; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany., Schirmacher P; Institute of Pathology, University Hospital, Heidelberg, Germany., Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Brenner H; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Hoffmeister M; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Haug U; Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany.; Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany., Owen RW; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Ulrich CM; Department of Population Health Sciences, University of Utah, Salt Lake City, Utah. neli.ulrich@hci.utah.edu.; Huntsman Cancer Institute, Salt Lake City, Utah.; Fred Hutchinson Cancer Research Center, Seattle, Washington.
Jazyk:	angličtina
Zdroj:	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2020 Feb; Vol. 29 (2), pp. 460-469. Date of Electronic Publication: 2019 Nov 18.
DOI:	10.1158/1055-9965.EPI-19-0449
Abstrakt:	Background: Xenobiotic-metabolizing enzymes (XME) play a critical role in the activation and detoxification of several carcinogens. However, the role of XMEs in colorectal carcinogenesis is unclear. Methods: We investigated the expression of XMEs in human colorectal tissues among patients with stage I-IV colorectal cancer ( n = 71) from the ColoCare Study. Transcriptomic profiling using paired colorectal tumor and adjacent normal mucosa tissues of XMEs ( GSTM1, GSTA1, UGT1A8, UGT1A10, CYP3A4, CYP2C9 , GSTP1 , and CYP2W1 ) by RNA microarray was compared using Wilcoxon rank-sum tests. We assessed associations between clinicopathologic, dietary, and lifestyle factors and XME expression with linear regression models. Results: GSTM1, GSTA1, UGT1A8, UGT1A10 , and 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 with men (β = 0.37, P = 0.02). By tumor site, CYP2C9 expression was lower in normal mucosa among patients with rectal cancer versus colon cancer cases (β = -0.21, P = 0.0005). Smokers demonstrated higher CYP2C9 expression levels in normal mucosa (β = 0.17, P = 0.02) when compared with nonsmokers. Individuals who used NSAIDs had higher GSTP1 tumor expression compared with non-NSAID users (β = 0.17, P = 0.03). Higher consumption of cooked vegetables (>1×/week) was associated with higher CYP3A4 expression in colorectal tumor tissues (β = 0.14, P = 0.007). Conclusions: XMEs have lower expression in colorectal tumor relative to normal mucosa tissues and may modify colorectal carcinogenesis via associations with clinicopathologic, lifestyle, and dietary factors. Impact: Better understanding into the role of drug-metabolizing enzymes in colorectal cancer may reveal biological differences that contribute to cancer development, as well as treatment response, leading to clinical implications in colorectal cancer prevention and management. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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