The association of previous cancer history with the incidence of prostate cancer harboring germline mutations.

Abstract

e17142 Background: Prostate Cancer (PCa) is the most common cancer in men and is the second leading cause of cancer-related mortality in men in the USA. It is estimated that 10-15% of PCa cases are due to germline mutations. PCa with germline mutation is generally more biologically aggressive and is associated with worse clinical outcomes. Therefore, it is crucial to understand factors that may influence the risk of PCa with germline mutations. We assessed the impact of a prior cancer diagnosis. Methods: Data were extracted from the Myriad Collaborative Research Registry (MCRR) for patients with a PCa diagnosis who received germline testing (MyRisk; starting September 2013) through Myriad Genetics. Variables included age of diagnosis, family and personal history of cancer, USA region, and germline mutation status. Patients were categorized based on whether they had no prior cancer diagnosis, one prior diagnosis, or 2+ prior diagnoses. A logistic regression model assessed the factors associated with a positive germline mutation. Results: The total number of PCa patients in the study was 42,643. Overall, 12.4% of PCa patients tested positive for a germline mutation. 10.5% of patients with no prior cancer history had a positive germline mutation, significantly less than the 15.1% of patients with one previous diagnosis (p<0.001) and 17.5% with 2+ previous diagnoses (p<0.001). The most significant difference was seen in patients with a history of colon cancer, where 8.6% of those with a positive germline mutation previously had colon cancer, while only 5.3% of those negative for a germline mutation did (p<0.001). In the logistic regression model (Table 1), a prior diagnosis of ureteral cancer (OR: 5.61, CI: 2.33-13.5), bladder cancer (OR: 1.53, CI: 1.19-1.97), sarcoma (OR: 2.51, CI: 1.15-5.50), and colon cancer (OR: 1.53, CI: 1.37-1.72) was statistically significantly associated with a germline mutation. Conclusions: PCa harboring germline mutations is associated with a prior diagnosis of cancer, specifically genitourinary cancers such as bladder and ureteral cancer, as well as colon cancer and sarcomas. These results emphasize the need to perform germline mutation testing in patients with a prior cancer history. Multivariable logistic regression model assessing associations of various factors with positive germline mutations in PCa patients. OR CI (95%) p-value Father had cancer 0.96 0.86-1.07 0.46 Sibling had cancer 0.98 0.88-1.09 0.69 Mother had cancer 1.03 0.92-1.15 0.62 Had bladder cancer 1.53 1.19-1.97 <0.001 Had ureteral cancer 5.61 2.33-13.5 <0.001 Had kidney/renal cancer 1.06 0.79-1.44 0.69 Had lung cancer 1.33 0.88-1.99 0.18 Had colon cancer 1.53 1.37-1.72 <0.001 Had sarcoma 2.51 1.15-5.50 0.02 *The multivariable model also adjusted for USA region of residence, age, and other cancers (Leukemia, lymphoma, head and neck, brain, melanoma, pancreatic, small bowel, gastric cancer, and other cancers).