2018 ASCO Annual Meeting!
Session: Genitourinary (Prostate) Cancer
Type: Poster Session
Time: Saturday June 2, 1:15 PM to 4:45 PM
Location: Hall A
The association of BRCA1 and BRCA2 mutations on prostate cancer risk, frequency, and mortality: Systematic review and meta-analysis.
Genitourinary (Prostate) Cancer
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #287)
J Clin Oncol 36, 2018 (suppl; abstr 5060)
Author(s): Mok Oh, Rana Aljadeed, Nasser Mubarak Al Khushaym, Abdulhamid Althagafi, Saad Fallatah, Hani M. Babiker, Ali McBride, Ivo Abraham; University of Arizona College of Pharmacy, Tucson, AZ; University of Arizona Cancer Center, Tucson, AZ
Background: A prior meta-analysis (Fachal, Prostate, 2011) suggested no association between BRCA1 mutation and prostate cancer (PCa). Several additional BRCA2 studies have shown an association with PCa risk and mortality. We conducted a systematic review and meta-analysis of BRCA1 and BRCA2 studies to estimate PCa risk in BRCA mutation carriers, evaluate the frequency of BRCA mutation carriers in PCa patients (pts) and compare survival rate among BRCA mutation carriers and non-carriers. Methods: PubMed/MEDLINE, Embase and Cochrane databases were searched for relevant studies for the above objectives. Meta-analyses were conducted using unadjusted odds ratio (OR) with 95% confidence interval (95%CI) for PCa incidence; frequency (%) of BRCA mutation in PCa pts; and hazard ratio (HR) with 95%CI for cancer-specific survival (CSS) and overall survival (OS). Random effects analyses were performed for overall BRCA (BRCA1 or BRCA2), with subgroup analyses for BRCA1 and BRCA2 separately. Results: 10 cohort, 10 case-control, 38 frequency and 11 survival studies were included. Being a BRCA carrier was associated with a significant increase in PCa risk (OR 1.97, 95%CI 1.60-2.42), with BRCA2 mutation being associated with a greater risk of PCa (OR 2.72, 95%CI 2.10-3.54) than BRCA1 (OR 1.39, 95%CI 1.07-1.81). The frequency of BRCA1 and BRCA2 carriers in PCa patients was 1.8% and 2.7% respectively. OS (HR 2.21, 95%CI 1.64-2.30) and CSS (HR 2.63, 95%CI 2.00-3.45) were significantly worse among BRCA2 carriers compared to non-carriers, whereas OS (HR 0.47, 95%CI 0.11-1.99) and CSS (HR 1.07, 95%CI 0.38-2.96) were not statistically significant when comparing BRCA1 carriers and non-carriers. Conclusions: Meta-analyses revealed a 1.97-fold greater risk of prostate cancer in overall BRCA mutation carriers. This elevated PCa risk was attributable largely to a 2.72-fold greater risk of PCa in BRCA2 carriers and a moderate 1.39-fold greater risk in BRCA1 carrier. BRCA2, but not BRCA1, mutations were associated with higher PCa mortality. BRCA mutation may be a clinical factor to stratify high-risk patients and provide clinical strategies for more effective targeted treatments for patients with PCa.