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Genome-wide association study of germline variants and breast cancer-specific mortality
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(2019) Genome-wide association study of germline variants and breast cancer-specific mortality. British Journal of Cancer, 120 (6). pp. 647-657. doi:10.1038/s41416-019-0393-x ISSN 0007-0920.
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Official URL: http://dx.doi.org/10.1038/s41416-019-0393-x
Abstract
Background:
We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.
Methods:
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).
Results:
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.
Conclusions:
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.
Item Type: | Journal Article | ||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Breast -- Cancer -- Genetics -- Research | ||||||
Journal or Publication Title: | British Journal of Cancer | ||||||
Publisher: | Nature Publishing Group | ||||||
ISSN: | 0007-0920 | ||||||
Official Date: | 21 February 2019 | ||||||
Dates: |
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Volume: | 120 | ||||||
Number: | 6 | ||||||
Page Range: | pp. 647-657 | ||||||
DOI: | 10.1038/s41416-019-0393-x | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 8 May 2019 | ||||||
Date of first compliant Open Access: | 9 May 2019 |
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