British journal of cancer, March 2019, Vol.120(6), pp.647-657
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. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10, 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, 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.
Chromosome 7 ; Bayesian Analysis ; Bayesian Analysis ; Confidence Intervals ; Breast Cancer ; Cancer ; Genomes ; Hoxa Gene ; Mortality ; Ribonucleic Acid–RNA ; Cancer ; Mortality ; Patients ; Breast Cancer ; Genomes ; Non-Coding RNA ; Breast ; Mortality ; Statistical Analysis ; Mathematical Models ; Breast Cancer ; Mortality;
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