Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness

• Verfasst von: Patel, Vivek L. [VerfasserIn]
• Verfasst von: Hamann, Ute [VerfasserIn]
• Verfasst von: Sutter, Christian [VerfasserIn]
• Titel: Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness
• Verf.angabe: Vivek L. Patel, Ute Hamann, Christian Sutter [und viele weitere]
• Jahr: 2020
• Jahr des Originals: 2019
• Umfang: 16 S.
• Fussnoten: Published online first: November 13, 2019 ; Gesehen am 07.04.2020
• Titel Quelle: Enthalten in: Cancer research
• Ort Quelle: Philadelphia, Pa. : AACR, 1916
• Jahr Quelle: 2020
• Band/Heft Quelle: 80(2020), 3, Seite 624-638
• ISSN Quelle: 1538-7445
• DOI: doi:10.1158/0008-5472.CAN-19-1840
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1694191451

Abstract

<h3></h3> <p>Pathogenic sequence variants (PSV) in <i>BRCA1</i> or <i>BRCA2</i> (<i>BRCA1/2</i>) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in <i>BRCA1/2</i> were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 <i>BRCA1</i> and 171 <i>BRCA2</i> male PSV carriers with prostate cancer, and 3,388 <i>BRCA1</i> and 2,880 <i>BRCA2</i> male PSV carriers without prostate cancer. PSVs in the 3′ region of <i>BRCA2</i> (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; <i>P</i> = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; <i>P</i> = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; <i>P</i> = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; <i>P</i> = 0.0002). No genotype-phenotype associations were detected for PSVs in <i>BRCA1</i>. These results demonstrate that specific <i>BRCA2</i> PSVs may be associated with elevated risk of developing aggressive prostate cancer.</p><h3>Significance:</h3> <p>Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.</p>