Kadalayil, Latha, Khan, Sofia, Nevanlinna, Heli, Fasching, Peter, Couch, Fergus, Hopper, John, Liu, Jianjun, Maishman, Thomas, Durcan, Lorraine, Gerty, Sue, Blomqvist, Carl, Rack, Brigitte, Janni, Wolfgang, Collins, Andrew, Eccles, Diana and Tapper, William (2017) Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women. Nature Communications, 8 (1), [1632]. (doi:10.1038/s41467-017-01775-y).
Abstract
To identify genetic variants associated with breast cancer prognosis we conduct a meta-analysis of overall (OS) and disease-free survival (DFS) in 6,042 patients from four cohorts. In young women, breast cancer is characterised by a higher incidence of adverse pathological features, unique gene expression profiles and worse survival, which may relate to germline variation. To explore this hypothesis, we also perform survival analysis in 2,315 patients aged ≤40 at diagnosis. Here, we identify two SNPs associated with early onset DFS, rs715212 (Pmeta=3.54x10-5) and rs10963755 (Pmeta=3.91x10-4) in ADAMTSL1. The effect of these SNPs is independent of classical prognostic factors and there is no heterogeneity between cohorts. Most importantly, the association with rs715212 is noteworthy (FPRP<0.2) and approaches genome-wide significance in multivariable analysis (Pmultivariable=5.37x10-8). Expression quantitative trait analysis provides tentative evidence that rs715212 may influence AREG expression (PeQTL=0.035) although further functional studies are needed to confirm this association and determine a mechanism.
More information
Identifiers
Catalogue record
Export record
Altmetrics
Contributors
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.