Associations of environment, health history, T-zone lymphoma, and T-zone-like cells of undetermined significance: A case-control study of aged Golden Retrievers

Abstract

Background: T-zone lymphoma (TZL), an indolent disease in older dogs, comprises approximately 12% of lymphomas in dogs. TZL cells exhibit an activated phenotype, indicating the disease may be antigen-driven. Prior research found that asymptomatic aged Golden Retrievers (GLDRs) commonly have populations of T-zone-like cells (phenotypically identical to TZL) of undetermined significance (TZUS).

Objective: To evaluate associations of inflammatory conditions, TZL and TZUS, using a case-control study of GLDRs.

Animals: TZL cases (n = 140), flow cytometrically diagnosed, were identified through Colorado State University's Clinical Immunology Laboratory. Non-TZL dogs, recruited through either a database of owners interested in research participation or the submitting clinics of TZL cases, were subsequently flow cytometrically classified as TZUS (n = 221) or control (n = 147).

Methods: Health history, signalment, environmental, and lifestyle factors were obtained from owner-completed questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using multivariable logistic regression, obtaining separate estimates for TZL and TZUS (versus controls).

Results: Hypothyroidism (OR, 0.3; 95% CI, 0.1-0.7), omega-3 supplementation (OR, 0.3; 95% CI, 0.1-0.6), and mange (OR, 5.5; 95% CI, 1.4-21.1) were significantly associated with TZL. Gastrointestinal disease (OR, 2.4; 95% CI, 0.98-5.8) had nonsignificantly increased TZL odds. Two shared associations for TZL and TZUS were identified: bladder infection or calculi (TZL OR, 3.5; 95% CI, 0.96-12.7; TZUS OR, 5.1; 95% CI, 1.9-13.7) and eye disease (TZL OR, 2.3; 95% CI, 0.97-5.2; TZUS OR, 1.9; 95% CI, 0.99-3.8).

Conclusions and clinical importance: These findings may elucidate pathways involved in TZUS risk and progression from TZUS to TZL. Further investigation into the protective association of omega-3 supplements is warranted.

Keywords: dog; epidemiology; lymphosarcoma; noninfectious diseases; oncology; statistical modeling.

Figure 1

Diagram of recruitment and study population. TZL cases were recruited from veterinary clinics throughout the U.S. Lymphoma‐free GLDRs aged 9 years and older were recruited from both veterinary clinics and the Canine Lifetime Health Project database as the comparison group. All dogs recruited for the comparison group were tested via flow cytometry for designation as either TZUS or control. Recruitment strategies were subsequently combined based on flow cytometric categorization to create 3 groups: TZL, TZUS, and controls.

Figure 2

State of residence for 508 dogs enrolled in the study. Not depicted: 2 dogs from Canada, 1 with unknown zip code of residence, and 2 with invalid zip codes

Figure 3

Flowchart of variables selected based on criteria to be assessed in multivariable modeling, best subsets, and backward selection

Figure 4

Final multivariable modeling results for TZL versus control model and TZUS versus control model. Odds ratios (ORs) and 95% confidence intervals (CIs) are shown in log scale. Age at spay or neuter and DHPP vaccination frequency were included in the TZL versus control model as indicators of selection bias, so their ORs are not shown in this figure