Response of glutathione <i>S</i>‐transferase Pi (GSTP1) to neoadjuvant therapy in rectal adenocarcinoma

Bedford, Matthew; Anathhanam, S.; Saleh, Daniel; Hickson, A.; McGregor, Alan; Boyle, K.; Burke, Dermot

doi:10.1111/j.1463-1318.2012.03022.x

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…For phase II enzymes, we report here that the expression of most GSTs and UGTs (GSTM1, GSTA1, UGT1A8, and UGT1A10) was significantly lower in colorectal tumor relative to normal mucosa tissues among patients with colorectal cancer. In contrast, we noted that GSTP1 expression was significantly higher in colorectal tumor versus normal mucosa tissues among patients with colorectal cancer-aligned with previous studies that have reported significant increases in GSTP1 mRNA and/ or protein expression in colorectal cancer, as well as in aberrant crypt foci, precursor lesions of colorectal cancer (20)(21)(22)(23)(53)(54)(55). By patient sex, we also found higher expression of GSTM1 in normal tissues among women compared with men.…”

Section: Discussionsupporting

confidence: 89%

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

Beyerle

Holowatyj

Haffa

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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 ¼ 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 (b ¼ 0.37, P ¼ 0.02). By tumor site, CYP2C9 expression was lower in normal mucosa among patients with rectal cancer versus colon cancer cases (b ¼ À0.21, P ¼ 0.0005). Smokers demonstrated higher CYP2C9 expression levels in normal mucosa (b ¼ 0.17, P ¼ 0.02) when compared with nonsmokers. Individuals who used NSAIDs had higher GSTP1 tumor expression compared with non-NSAID users (b ¼ 0.17, P ¼ 0.03). Higher consumption of cooked vegetables (>1Â/week) was associated with higher CYP3A4 expression in colorectal tumor tissues (b ¼ 0.14, P ¼ 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 drugmetabolizing 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.

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Section: Discussionsupporting

confidence: 89%

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

Beyerle

Holowatyj

Haffa

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

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Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer

Beyerle

Frei

Stiborová

et al. 2015

Drug Metabolism Reviews

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In humans, the liver is generally considered to be the major organ contributing to drug metabolism, but studies during the last years have suggested an important role of the extra-hepatic drug metabolism. The gastrointestinal tract (GI-tract) is the major path of entry for a wide variety of compounds including food, and orally administered drugs, but also compounds - with neither nutrient nor other functional value - such as carcinogens. These compounds are metabolized by a large number of enzymes, including the cytochrome P450 (CYP), the glutathione S-transferase (GST) family, the uridine 5'-diphospho- glucuronosyltransferase (UDP-glucuronosyltransferase - UGT) superfamily, alcohol-metabolizing enzymes, sulfotransferases, etc. These enzymes can either inactivate carcinogens or, in some cases, generate reactive species with higher reactivity compared to the original compound. Most data in this field of research originate from animal or in vitro studies, wherein human studies are limited. Here, we review the human studies, in particular the studies on the phenotypic expression of these enzymes in the colon and rectum to get an impression of the actual enzyme levels in this primary organ of exposure. The aim of this review is to give a summary of currently available data on the relation between the CYP, the GST and the UGT biotransformation system and colorectal cancer obtained from clinical and epidemiological studies in humans.

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Response of glutathione S‐transferase Pi (GSTP1) to neoadjuvant therapy in rectal adenocarcinoma

Abstract: The GSTP1 level is increased in rectal adenocarcinoma compared with adjacent normal mucosa. It decreases following neoadjuvant therapy. Future studies correlating pre-therapy GSTP1 levels with pathological response would be of interest.

Cited by 2 publications

References 33 publications

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

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

Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer

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