Dataset Information

Glutathione S-transferase theta genotypes and environmental exposures in the risk of canine transitional cell carcinoma.

ABSTRACT:

Introduction

Transitional cell carcinoma (TCC) in humans is associated with environmental exposures and variants in glutathione S-transferase (GST) genes. Scottish Terriers have a high breed risk for TCC, but the relationship between genetic and environmental risk in dogs is not fully understood.

Hypotheses

Scottish Terriers have a higher frequency of GST-theta variants compared to lower risk breeds. Dogs with TCC of any breed have a higher frequency of GST-theta variants along with higher environmental exposures, compared to controls.

Animals

One hundred and five Scottish Terriers and 68 controls from lower risk breeds; 69 dogs of various breeds with TCC, and 72 breed- and sex-matched unaffected geriatric dogs.

Methods

In this prospective case-control study, dogs were genotyped for 3 canine GST-theta variants: GSTT1 I2+28 G>A, a GSTT1 3'UTR haplotype, and GSTT5 Asp129_Gln130del. Owners of dogs with TCC and unaffected geriatric controls completed a household environmental questionnaire.

Results

The GSTT1 3'UTR haplotype and GSTT5 Asp129_Gln130del variants were significantly underrepresented in Scottish Terriers (minor allele frequency [MAF] = 0.000 for both), compared to dogs from lower risk breeds (MAF = 0.108 and 0.100; P ≤ .0002). Dogs with TCC did not differ from unaffected geriatric controls across the 3 investigated loci. Transitional cell carcinoma was associated with household insecticide use (odds ratio [OR] = 4.28, 95% confidence interval [CI] = 1.44-12.33, P = .02), and was negatively associated with proximity to a farm (OR = 0.49, 95% CI = 0.25-0.99, P = .04).

Conclusions and clinical importance

Low-activity GST-theta loci are unlikely contributors to TCC risk in dogs. Increased risk is associated with household insecticide use, and possibly with less rural households.

SUBMITTER: Luethcke KR

PROVIDER: S-EPMC6524089 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Glutathione S-transferase theta genotypes and environmental exposures in the risk of canine transitional cell carcinoma.

Luethcke Katherine R KR Ekena Joanne J Chun Ruthanne R Trepanier Lauren A LA

Journal of veterinary internal medicine 20190422 3

<h4>Introduction</h4>Transitional cell carcinoma (TCC) in humans is associated with environmental exposures and variants in glutathione S-transferase (GST) genes. Scottish Terriers have a high breed risk for TCC, but the relationship between genetic and environmental risk in dogs is not fully understood.<h4>Hypotheses</h4>Scottish Terriers have a higher frequency of GST-theta variants compared to lower risk breeds. Dogs with TCC of any breed have a higher frequency of GST-theta variants along wi ...[more]

PMID: 31008543

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Project description:BackgroundGlutathione (GSH) is one of the most important agents of the antioxidant defense system of the cell because, in conjunction with the enzymes glutathione peroxidase (GSH-Px) and glutathione S transferase pi (GSTpi), it plays a central role in the detoxification and biotransformation of chemotherapeutic drugs. This study evaluated the expression of GSH and the GSH-Px and GSTpi enzymes by immunohistochemistry in 30 canine mammary tumors, relating the clinicopathological parameters, clinical outcome and survival of the bitches. In an in vitro study, the expression of the genes glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS) that synthesize GSH and GSH-Px gene were verified by qPCR and subjected to treatment with doxorubicin, to check the resistance of cancer cells to chemotherapy.ResultsThe immunohistochemical expression of GSH, GSH-Px and GSTpi was compared with the clinical and pathological characteristics and the clinical outcome in the bitches, including metastasis and death.The results showed that high immunoexpression of GSH was correlated to the absence of tumor ulceration and was present in dogs without metastasis (P < 0.05). There was significant correlation of survival with the increase of GSH (P < 0.05). The expression of the GSH-Px and GSTpi enzymes showed no statistically significant correlation with the analyzed variables (p > 0.05). The analysis of the relative expression of genes responsible for the synthesis of GSH (GCLC and GSS) and GSH-Px by quantitative PCR was done with cultured cells of 10 tumor fragments from dogs with mammary tumors.The culture cells showed a decrease in GCLC and GSS expression when compared with no treated cells (P < 0.05). High GSH immunoexpression was associated with better clinical outcomes.ConclusionTherefore, high expression of the GSH seems to play an important role in the clinical outcome of patients with mammary tumors and suggest its use as prognostic marker. The in vitro doxorubicin treatment significantly reduces the expression of GCLC and GSS genes so we can consider them to be candidates for predictive markers of therapeutic response in mammary cancer.

Dataset Information

Glutathione S-transferase theta genotypes and environmental exposures in the risk of canine transitional cell carcinoma.

Introduction

Hypotheses

Animals

Methods

Results

Conclusions and clinical importance

Publications

Glutathione S-transferase theta genotypes and environmental exposures in the risk of canine transitional cell carcinoma.

Similar Datasets

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