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Positive association between a glutathione‐ S ‐transferase polymorphism and lymphoma in dogs
Author(s) -
Ginn J.,
Sacco J.,
Wong Y. Y.,
MotsingerReif A.,
Chun R.,
Trepanier L. A.
Publication year - 2014
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12000
Subject(s) - lymphoma , genotype , odds ratio , biology , glutathione s transferase , exon , genotyping , canine lymphoma , medicine , genetics , glutathione , oncology , immunology , gene , enzyme , biochemistry
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.