Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women

Latha Kadalayil, Sofia Khan, Heli Nevanlinna, Peter A. Fasching, Fergus J. Couch, John L. Hopper, Jianjun Liu, Tom Maishman, Lorraine Durcan, Sue Gerty, Carl Blomqvist, Brigitte Rack, Wolfgang Janni, Andrew Collins, Diana Eccles and William Tapper ()
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Latha Kadalayil: University of Southampton, Southampton General Hospital
Sofia Khan: University of Helsinki and Helsinki University Hospital
Heli Nevanlinna: University of Helsinki and Helsinki University Hospital
Peter A. Fasching: University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN
Fergus J. Couch: Mayo Clinic
John L. Hopper: The University of Melbourne, Melbourne
Jianjun Liu: Genome Institute of Singapore
Tom Maishman: University of Southampton and University Hospital Southampton NHS Foundation Trust
Lorraine Durcan: University of Southampton and University Hospital Southampton NHS Foundation Trust
Sue Gerty: University of Southampton and University Hospital Southampton NHS Foundation Trust
Carl Blomqvist: Helsinki University Central Hospital
Brigitte Rack: University Ulm, Prittwitzstrasse 43
Wolfgang Janni: University Ulm, Prittwitzstrasse 43
Andrew Collins: University of Southampton, Southampton General Hospital
Diana Eccles: University of Southampton, Southampton University Hospitals NHS Trust
William Tapper: University of Southampton, Southampton General Hospital

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract To identify genetic variants associated with breast cancer prognosis we conduct a meta-analysis of overall survival (OS) and disease-free survival (DFS) in 6042 patients from four cohorts. In young women, breast cancer is characterized 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 2315 patients aged ≤ 40 years at diagnosis. Here, we identify two SNPs associated with early-onset DFS, rs715212 (P meta = 3.54 × 10−5) and rs10963755 (P meta = 3.91 × 10−4) 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

Date: 2017
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DOI: 10.1038/s41467-017-01775-y

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