Genome-wide association study of germline variants and breast cancer-specific mortality

• Verfasst von: Escala-Garcia, Maria [VerfasserIn]
• Verfasst von: Arndt, Volker [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Burwinkel, Barbara [VerfasserIn]
• Verfasst von: Canzian, Federico [VerfasserIn]
• Verfasst von: Chang-Claude, Jenny [VerfasserIn]
• Verfasst von: Hamann, Ute [VerfasserIn]
• Verfasst von: Kaaks, Rudolf [VerfasserIn]
• Verfasst von: Schneeweiss, Andreas [VerfasserIn]
• Verfasst von: Sohn, Christof [VerfasserIn]
• Verfasst von: Zhang, Yan [VerfasserIn]
• Titel: Genome-wide association study of germline variants and breast cancer-specific mortality
• Verf.angabe: Maria Escala-Garcia, Volker Arndt, Hermann Brenner, Barbara Burwinkel, Federico Canzian, Jenny Chang-Claude, Ute Hamann, Rudolf Kaaks, Andreas Schneeweiss, Christof Sohn, Yan Zhang [und 225 weitere]
• E-Jahr: 2019
• Jahr: 21 February 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 25.06.2019
• Titel Quelle: Enthalten in: British journal of cancer
• Ort Quelle: Edinburgh : Nature Publ. Group, 1999
• Jahr Quelle: 2019
• Band/Heft Quelle: 120(2019), 6, Seite 647-657
• ISSN Quelle: 1532-1827
• DOI: doi:10.1038/s41416-019-0393-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 166788929X

Abstract

We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10−8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.