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.

Risk of bladder cancer and lymphoma in dogs is associated with pollution indices by county of residence

“…County of residence data were available for 66 of 69 dogs with UCC of the bladder or urethra and 70 of 72 unaffected controls of comparable sex and breed ≥11 years old 24 . At the time of original enrolment, dogs with UCC resided in 42 individual counties across 19 states, and control dogs resided in 41 counties across 18 states (Table 1).…”

Comparative Analysis of the Glutathione S-Transferase Gene Family of Four Triticeae Species and Transcriptome Analysis of GST Genes in Common Wheat Responding to Salt Stress

“…Compared to the control group, statistically significant differences referenced to * P < 0:05 and * * P < 0:01 by Student's t-test. 8 International Journal of Genomics evolution and the higher prevalence of duplication events possibly facilitating rapid adaptation to different environmental conditions.…”

“…Among the ten classes, Tau and Phi GSTs are plant-specific and the most abundant [ 6 ]; they play vital roles in metabolizing xenobiotics. Zeta and Theta class GSTs have been highly conserved over a long evolutionary period and have very restricted activities toward xenobiotics [ 7 , 8 ]. Both DHAR and Lambda class GSTs function as thiol transferases, by replacing their serine residue with cysteine [ 1 , 9 , 10 ].…”

Genetic and environmental risk for lymphoma in boxer dogs

“…Our findings were limited somewhat by group sizes and by constraints inherent in questionnaire‐based epidemiologic studies. Our questionnaire was developed for the present study and another study on cancer risk in dogs, 52 and was not independently validated. Some owners seemed unsure about what chemicals and water treatments were used in their homes, and some of the questionnaire assessments were subjective, such as rural vs suburban or urban.…”