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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F20%3A10422302" target="_blank" >RIV/00216208:11310/20:10422302 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=X8-.57exrn" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=X8-.57exrn</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1055-9965.EPI-19-0449" target="_blank" >10.1158/1055-9965.EPI-19-0449</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 dinicopathologic, 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 &lt;= 0.03). Women had significantly higher expression of GSTM1 in normal tissues compared with men (beta = 0.37, P = 0.02). By tumor site, CYP2C9 expression was lower in normal mucosa among patients with rectal cancer versus colon cancer cases (beta = -0.21, P = 0.0005). Smokers demonstrated higher CYP2C9 expression levels in normal mucosa (beta = 0.17, P = 0.02) when compared with non- smokers. Individuals who used NSAIDs had higher GSTP1 tumor expression compared with non-NSAID users (beta = 0.17, P = 0.03). Higher consumption of cooked vegetables (&gt;1 x /week) was associated with higher CYP3A4 expression in colorectal tumor tissues (beta = 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 dinicopathologic, 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 &lt;= 0.03). Women had significantly higher expression of GSTM1 in normal tissues compared with men (beta = 0.37, P = 0.02). By tumor site, CYP2C9 expression was lower in normal mucosa among patients with rectal cancer versus colon cancer cases (beta = -0.21, P = 0.0005). Smokers demonstrated higher CYP2C9 expression levels in normal mucosa (beta = 0.17, P = 0.02) when compared with non- smokers. Individuals who used NSAIDs had higher GSTP1 tumor expression compared with non-NSAID users (beta = 0.17, P = 0.03). Higher consumption of cooked vegetables (&gt;1 x /week) was associated with higher CYP3A4 expression in colorectal tumor tissues (beta = 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer Epidemiology, Biomarkers &amp; Prevention

ISSN

1055-9965

e-ISSN

—

Svazek periodika

29

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

460-469

Kód UT WoS článku

000521285500023

EID výsledku v databázi Scopus

2-s2.0-85079077387