Genome-wide association study of germline variants and breast cancer-specific mortality
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 even...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
21 February 2019
|
| In: |
British journal of cancer
Year: 2019, Jahrgang: 120, Heft: 6, Pages: 647-657 |
| ISSN: | 1532-1827 |
| DOI: | 10.1038/s41416-019-0393-x |
| Online-Zugang: | Verlag, Pay-per-use, Volltext: https://doi.org/10.1038/s41416-019-0393-x Verlag, Pay-per-use, Volltext: https://www.nature.com/articles/s41416-019-0393-x 
|
| Verfasserangaben: | 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] |
| Zusammenfassung: | 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. |
|---|---|
| Beschreibung: | Gesehen am 25.06.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 1532-1827 |
| DOI: | 10.1038/s41416-019-0393-x |