Abstract 3429: Evidence chronic inflammation is a risk factor for histiocytic sarcoma in Bernese mountain dogs - implications for human histiocytic sarcoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.3429-3429
• Main Authors: Ruple-Czerniak, Audrey, Morley, Paul S.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-3429

The purpose of this study was to evaluate exposure variables associated with development of histiocytic sarcoma (HS), a rare but aggressive malignancy, using the canine spontaneous tumor model. The domestic dog has been shown to be an excellent model to investigate risk of occurrence of complex diseases in humans, especially cancers. This is due in part to the limited genetic heterogeneity within specific dog breeds. HS, though rare in most breeds of dogs, is a common malignancy in Bernese mountain dogs (BMD) with up to 25% of the population of dogs being diagnosed with HS during their lifetime. The frequency of HS diagnosis in BMDs is thought to be due to a heritable mutation in a single gene region analogous to the human chromosome 9p21. For this study, owners of BMDs registered with a non-profit breed registry, the Berner-Garde Foundation, were recruited for participation in an internet-based cross-sectional survey. Data were collected for a total of 216 BMDs. Of the total population of BMDs enrolled in the study 118 dogs were sibling-sets representing a case and a non-case that originated from the same litter. Mixed effects logistic regression (MELR) and conditional logistic regression (CLR) were used in parallel to examine associations between potential risk factors and the occurrence of HS. When controlling for litter of origin (as a marker of relatedness), dogs diagnosed with orthopedic conditions were found to be more likely to develop HS (MELR, OR: 2.5, 95% CI: 1.5, 5.2; CLR, OR: 2.81, 95% CI: 1.1, 7.3), while dogs receiving prescription anti-inflammatory medications were found to be at a considerably lower risk of developing this disease (MELR, OR: 0.43, 95% CI: 0.2, 0.8; CLR, OR: 0.32, 95% CI: 0.1, 0.8). These data suggest inflammation may be a modifiable risk factor for the development of HS. Therefore, identification and treatment of conditions that promote inflammatory mechanisms may reduce future risk of developing HS in dogs and people. Results of logistic regression models examining risk factors associated with development of histiocyRisk factorCategoryOdds ratio (MELR), n = 21695% CIP-ValueOdds ratio (CLR), n = 11895% CIP-ValueOrthopedic conditionYes2.491.21, 5.140.0142.811.08, 7.260.034NoReferenceReferenceNon-prescription medication useYes2.101.05, 4.180.0362.881.04, 7.900.041NoReferenceReferenceLong-term prescription medication useYes0.430.22, 0.810.0100.320.12, 0.830.020NoReferenceReference Citation Format: Audrey Ruple-Czerniak, Paul