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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

Cancer Epidemiology, Biomarkers &amp; Prevention

ISSN

1055-9965

e-ISSN

—

Volume of the periodical

29

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

460-469

UT code for WoS article

000521285500023

EID of the result in the Scopus database

2-s2.0-85079077387