Mok Oh1, Nasser Alkhushaym1,2, Saad Fallatah1,3, Abdulhamid Althagafi1,4, Rana Aljadeed1,5, Yazed Alsowaida1,6, Joanne Jeter7, Jennifer R Martin8, Hani M Babiker9,10, Ali McBride10,11, Ivo Abraham11,12. 1. Department of Pharmacy Practice & Science, Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, University of Arizona, Tucson, Arizona. 2. Department of Clinical Pharmacy, Royal Commission Health Services Program, Jubail, Saudi Arabia. 3. Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Medina, Saudi Arabia. 4. Department of Clinical Pharmacy, College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. 5. Department of Pharmacy, Houston Methodist Hospital, Houston, Texas. 6. Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail, Saudi Arabia. 7. Departments of Human Genetics and Medical Oncology, College of Medicine, The Ohio State University, Columbus, Ohio. 8. Department of Pharmacy Practice and Science, College of Pharmacy, Arizona Health Sciences Library, University of Arizona, Tucson, Arizona. 9. Department of Hematology & Oncology, College of Medicine, Banner University Medical Center, University of Arizona Cancer Center, Tucson, Arizona. 10. Department of Pharmacy Practice and Science, College of Pharmacy, Banner University Medical Center, University of Arizona Cancer Center, Tucson, Arizona. 11. Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona. 12. Department of Family and Community Medicine, College of Medicine, University of Arizona, Tucson, Arizona.
Abstract
BACKGROUND: A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests. RESULTS: A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, 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 noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. CONCLUSIONS: There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa.
BACKGROUND: A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests. RESULTS: A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, 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 noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. CONCLUSIONS: There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa.
Authors: Shuai Li; Valentina Silvestri; Goska Leslie; Timothy R Rebbeck; Susan L Neuhausen; John L Hopper; Henriette Roed Nielsen; Andrew Lee; Xin Yang; Lesley McGuffog; Michael T Parsons; Irene L Andrulis; Norbert Arnold; Muriel Belotti; Åke Borg; Bruno Buecher; Saundra S Buys; Sandrine M Caputo; Wendy K Chung; Chrystelle Colas; Sarah V Colonna; Jackie Cook; Mary B Daly; Miguel de la Hoya; Antoine de Pauw; Hélène Delhomelle; Jacqueline Eason; Christoph Engel; D Gareth Evans; Ulrike Faust; Tanja N Fehm; Florentia Fostira; George Fountzilas; Megan Frone; Vanesa Garcia-Barberan; Pilar Garre; Marion Gauthier-Villars; Andrea Gehrig; Gord Glendon; David E Goldgar; Lisa Golmard; Mark H Greene; Eric Hahnen; Ute Hamann; Helen Hanson; Tiara Hassan; Julia Hentschel; Judit Horvath; Louise Izatt; Ramunas Janavicius; Yue Jiao; Esther M John; Beth Y Karlan; Sung-Won Kim; Irene Konstantopoulou; Ava Kwong; Anthony Laugé; Jong Won Lee; Fabienne Lesueur; Noura Mebirouk; Alfons Meindl; Emmanuelle Mouret-Fourme; Hannah Musgrave; Joanne Ngeow Yuen Yie; Dieter Niederacher; Sue K Park; Inge Sokilde Pedersen; Juliane Ramser; Susan J Ramus; Johanna Rantala; Muhammad U Rashid; Florian Reichl; Julia Ritter; Andreas Rump; Marta Santamariña; Claire Saule; Gunnar Schmidt; Rita K Schmutzler; Leigha Senter; Saba Shariff; Christian F Singer; Melissa C Southey; Dominique Stoppa-Lyonnet; Christian Sutter; Yen Tan; Soo Hwang Teo; Mary Beth Terry; Mads Thomassen; Marc Tischkowitz; Amanda E Toland; Diana Torres; Ana Vega; Sebastian A Wagner; Shan Wang-Gohrke; Barbara Wappenschmidt; Bernhard H F Weber; Drakoulis Yannoukakos; Amanda B Spurdle; Douglas F Easton; Georgia Chenevix-Trench; Laura Ottini; Antonis C Antoniou Journal: J Clin Oncol Date: 2022-01-25 Impact factor: 50.717
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