Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome and genetic determinants of vitamin D insufficiency
Carcinogenesis (2012), doi: 10.1093/carcin/bgs187; Received November 29, 2011; First published online: May 23, 2012
Sigrid Hatse*,1, Diether Lambrechts2, Annemieke Verstuyf3, Ann Smeets4, Barbara Brouwers1, Thijs Vandorpe4, Olivier Brouckaert4, Gilian Peuteman2, Annouschka Laenen5, Lieve Verlinden3, Carsten Kriebitzsch3, Anne-Sophie Dieudonné4, Robert Paridaens4, Patrick Neven4, Marie-Rose Christiaens4, Roger Bouillon3 and Hans Wildiers1
1 Catholic University Leuven and University Hospitals, Laboratory of Experimental Oncology and Department of General Medical Oncology, Leuven, Belgium
2 Catholic University of Leuven, Vesalius Research Center, Leuven, Belgium
3 Catholic University of Leuven, Laboratory of Experimental Medicine and Endocrinology, Leuven, Belgium
4 University Hospitals Leuven, Multidisciplinary Breast Center, Leuven, Belgium
5 Catholic University of Leuven, Interuniversity Centre for Biostatistics and Statistical Bioinformatics, Leuven, Belgium
*Corresponding author Sigrid Hatse Contact email: sigrid.hatse at med.kuleuven.be Catholic University Leuven and University Hospitals, Laboratory of Experimental Oncology and Department of General Medical Oncology, Leuven, Belgium
Introduction: We correlated serum 25-hydroxyvitamin D3 (25OHD) levels with tumor characteristics and clinical disease outcome in breast cancer patients and assessed the impact of genetic determinants of vitamin D insufficiency.
Methods: We collected serum from 1800 early breast cancer patients at diagnosis, measured 25OHD by radioimmunoassay and determined genetic variants in vitamin D-related genes by Sequenom. Multivariable regression models were used to correlate 25OHD levels with tumor characteristics. Cox proportional hazard models were used to assess overall survival (OS), disease-specific survival (DSS) and disease-free interval (DFI).
Results: Lower 25OHD serum levels significantly correlated with larger tumor size at diagnosis (p=0.0063) but not with lymph node invasion, receptor status, or tumor grade. Genetic variants in 25-hydroxylase (CYP2R1) and vitamin D-binding protein significantly determined serum 25OHD levels but did not affect the observed association between serum 25OHD and tumor size.
High serum 25OHD (>30 ng/mL) at diagnosis significantly correlated with improved OS (p=0.0101) and DSS (p=0.0192) and additionally had a modest effect on DFI, which only became apparent after at least 3 years of follow-up.
When considering menopausal status, serum 25OHD had a strong impact on breast cancer-specific outcome in postmenopausal patients (hazards ratios for 25OHD >30 ng/mL versus ?30 ng/mL were 0.15 [p=0.0097] and 0.43 [p=0.0172] for DSS and DFI, respectively), whereas no association could be demonstrated in premenopausal patients.
Conclusion: High vitamin D levels at early breast cancer diagnosis correlate with lower tumor size and better OS, and improve breast cancer-specific outcome, especially in postmenopausal patients.
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