The Prostate 67:1174 ^1181 (2007) A Population Study of Neutering Status as a Risk Factor for Canine Prostate Cancer Jeffrey N. Bryan, 1 * Matthew R. Keeler, 1 Carolyn J. Henry, 1,3 Margaret E. Bryan, 2 Allen W. Hahn, 1 and Charles W. Caldwell 4 1 Department of Veterinary Medicine and Surgery,University of Missouri,Columbia, Missouri 2 Department of Statistics,University of Missouri,Columbia, Missouri 3 Department of Internal Medicine, Hematology/Oncology Division,University of Missouri,Columbia, Missouri 4 Department of Pathology and Anatomical Sciences,University of Missouri,Columbia, Missouri BACKGROUND. Prostate cancer has been reported to occur more commonly in neutered than intact male dogs in several case series. This study was undertaken to evaluate risk of prostate cancer in a large population database. The hypothesis was that castration is a risk factor for prostate cancer in male companion dogs. METHODS. Data were derived from recorded visits to North American veterinary teaching hospitals. The Veterinary Medical Databases (VMDB) were queried to yield male dogs with urinary bladder transitional cell carcinoma (TCC), prostate adenocarcinoma (ACA), prostate TCC, prostate carcinoma (CA), and prostate tumors. A second query yielded all male dogs over the age of 4 years without a diagnosis of urinary tract cancer. These populations were compared to determine relative risks for developing each disease, singly and collectively, associated with neutering status. Odds ratios were calculated for breed as a risk factor. RESULTS. Neutered males had a significantly increased risk for each form of cancer. Neutered males had an odds ratio of 3.56 (3.02–4.21) for urinary bladder TCC, 8.00 (5.60–11.42) for prostate TCC, 2.12 (1.80–2.49) for prostate adenocarcinoma, 3.86 (3.13–4.16) for prostate carcinoma, and 2.84 (2.57 – 3.14) for all prostate cancers. Relative risks were highly similar when cases were limited to those with a histologically confirmed diagnosis. CONCLUSIONS. Breed predisposition suggests that genetic factors play a role in the development of prostate cancer. The risk associated with being neutered is highest for TCC, supporting previous work identifying the urothelium and ductular rather than acinar epithelium as the source of these tumors. Prostate 67: 1174–1181, 2007. # 2007 Wiley-Liss, Inc. KEY WORDS: canine; prostate cancer; epidemiology; neutering; VMDB INTRODUCTION The American Cancer Society estimates that 232,090 men were diagnosed with prostate cancer and 30,350 men died of this disease in 2005. Anti-androgen therapy is the mainstay of treatment for the majority of these men, but often leads to a hormone-refractory tumor burden [1]. Hormone-refractory prostate cancer has a greater tendency to metastasize and is often resistant to cytotoxic chemotherapy [1,2]. For many years, mitoxantrone and prednisone were standard therapy, providing palliation for most patients as well as increased survival for the subset of men whose prostate-specific antigen (PSA) decreased after therapy [3]. Palliation of signs with benefit to a subset of patients is a similar response to that seen with mitoxantrone in dogs with transitional cell carcinoma (TCC) of the bladder [4]. Since 2004, docetaxel has become standard for treating men with metastatic, hormone-refractory prostate cancer [5,6]. This drug, too, has been the focus This work was presented in part at the 25th Annual Conference of the Veterinary Cancer Society *Correspondence to: Jeffrey N. Bryan, DVM, MS, DACVIM(Onc), 379 E. Campus Dr., Columbia, MO 65211. E-mail: bryanjn@missouri.edu Received 13 February 2007; Accepted 26 February 2007 DOI 10.1002/pros.20590 Published online 21 May 2007 in Wiley InterScience (www.interscience.wiley.com). ß 2007 Wiley-Liss, Inc.