Abstract 3449: Risk for death from prostate cancer predicted from complete family history of lethal prostate cancer

Abstract

Abstract Background: Familial relative risks (RR) for death from prostate cancer (lethal prostate cancer or LPC) are rare. Most risk estimations are for diagnosis of prostate cancer (PC); and typically focus on close relatives, rather than on complete family history. This study provides RRs for LPC based on specific family history data of LPC obtained from a statewide Cancer Registry linked to genealogy data. The risk estimates presented avoid common recall, recruitment, and ascertainment biases, and provide more individualized risk estimates. Methods: We used a population-based resource to estimate RRs for LPC based on a full constellation of family history of LPC. We include complete family history, taking into account degree of relationship (first to third-degree), age at diagnosis, paternal or maternal family history, number of affected individuals, and age at diagnosis of youngest relative. Estimations of RR for LPC based on specific family history are informative for patients and clinicians for appropriate screening decisions. The Utah Population Data Base (UPDB), a computerized population genealogical resource linked to a statewide SEER cancer registry, and statewide death certificates was analyzed. Over 1 million individuals were analyzed. All males with specific constellations of LPC were identified in the UPDB (probands) and the observed number of LPC cases among these probands was compared to the expected number using internal cohort-specific rates to obtain RR estimates. Results: Over 3,921 LPC cases were identified. Risk for LPC was significantly elevated with each additional LPC first-degree relative (FDR), ranging from RR = 2.26 (95% CI: 2.09, 2.44) for >0 FDRs to RR = 3.93 (1.69, 7.73) for >2 FDRs affected. Even in the absence of FDR family history, significantly increased risk for LPC was observed in the presence of >0 second degree relatives (SDR) affected (RR = 1.53: 1.41, 1.66). In the absence of affected FDRs and SDRs, there was significantly increased risk for LPC for >1 third degree relative (TDR) affected (RR = 1.22: 1.15, 1.29). Results indicated higher risks for maternal vs paternal history, e.g. RR = 1.50 (1.27, 1.76) for affected paternal uncle versus RR = 1.83 (1.59, 2.09) for affected maternal uncle. Discussion: RRs for LPC have more clinical significance than RRs for PC. This study provides unbiased, population-based estimates of LPC risk based on a man's specific family history LPC constellation. Many individuals at 2-3 times increased risk for dying from PC were identified based on family history. This study provides a means for containing healthcare costs and conserving resource utilization through informed use of familial LPC risks. Using informative LPC family history in the planning of screening, treatment, and monitoring opens additional avenues for implementation of more sound translational medicine practices, decreasing morbidity and mortality, and improving the quality of life in patients. Citation Format: Frederick S. Albright, Neeraj Agarwal, William T. Lowrance, Robert A. Stephenson, Lisa A. Cannon-Albright. Risk for death from prostate cancer predicted from complete family history of lethal prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3449. doi:10.1158/1538-7445.AM2015-3449