Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs. (29th September 2012)

• Record Type: Journal Article
• Authors: Ginn, J.; Sacco, J.; Wong, Y. Y.; Motsinger‐Reif, A.; Chun, R.; Trepanier, L. A.
• Is Part Of: Veterinary and comparative oncology. Volume 12:Number 3(2014:Sep.)
• Page Start: 227
• Page End: 236
• Publication Date: 2012-09-29
• Subjects: Veterinary oncology -- Periodicals; Neoplasms -- veterinary -- Periodicals; 636.0896994005
• DOI: 10.1111/vco.12000
• Languages: English
• ISSNs: 1476-5810

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Glutathione‐<italic>S</italic>‐transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over‐represented in human cancers; in particular, low activity <italic>GSTT1</italic> genotypes are risk factors for non‐Hodgkin lymphoma. We hypothesized that defective <italic>GSTT1</italic> genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3′‐UTR of canine <italic>GSTT1</italic> in dogs with lymphoma (<italic>n</italic> = 93) and age‐matched unaffected dogs (<italic>n</italic> = 86). Of 27 canine <italic>GSTT1</italic> variants identified, the I2+28 G&gt;A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77–22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (<italic>P</italic> = 0.002). This intronic variant was predicted to perturb <italic>GSTT1</italic> mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of <italic>GSTT1</italic> genotyping in epidemiologic studies of canine lymphoma risk.</p> </abstract>