title: Positive association between a glutathione-S-transferase polymorphism and lymphoma in dogs.
abstract: Glutathione-S-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 GSTT1 genotypes are risk factors for non-Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3'-UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age-matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>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 (P = 0.002). This intronic variant was predicted to perturb GSTT1 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 GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ginn
authors.forename: J
authors.initials: J
authors.lastname: Sacco
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Motsinger-Reif
authors.forename: R
authors.initials: R
authors.lastname: Chun
authors.forename: L A
authors.initials: LA
authors.lastname: Trepanier
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004283:Dog Diseases / Q000201:enzymology* / Q000235:genetics; D004285:Dogs; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D008223:Lymphoma / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D017354:Point Mutation; D011110:Polymorphism, Genetic
chemical_list: D005982:Glutathione Transferase