A common and functional gene variant in the vascular endothelial growth factor a predicts clinical outcome in early-stage breast cancer
Gudrun Absenger
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorJoanna Szkandera
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorMichael Stotz
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorMartin Pichler
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorThomas Winder
Department of Medicine, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
Search for more papers by this authorTanja Langsenlehner
Department of Therapeutic Radiology and Oncology, Medical University Graz, Graz, Austria
Search for more papers by this authorUwe Langsenlehner
Division of Internal Medicine, GKK Outpatient Department, Graz, Austria
Search for more papers by this authorHellmut Samonigg
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorWilfried Renner
Clinical Institute of Medical and Chemical Diagnostics, Medical University Graz, Graz, Austria
Search for more papers by this authorCorresponding Author
Armin Gerger
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Correspondence to: Research Unit: Genetic Epidemiology and Pharmacogenetics, Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Auenbruggerplatz 15, 8036 Graz, Austria.Search for more papers by this authorGudrun Absenger
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorJoanna Szkandera
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorMichael Stotz
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorMartin Pichler
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorThomas Winder
Department of Medicine, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
Search for more papers by this authorTanja Langsenlehner
Department of Therapeutic Radiology and Oncology, Medical University Graz, Graz, Austria
Search for more papers by this authorUwe Langsenlehner
Division of Internal Medicine, GKK Outpatient Department, Graz, Austria
Search for more papers by this authorHellmut Samonigg
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Search for more papers by this authorWilfried Renner
Clinical Institute of Medical and Chemical Diagnostics, Medical University Graz, Graz, Austria
Search for more papers by this authorCorresponding Author
Armin Gerger
Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
Correspondence to: Research Unit: Genetic Epidemiology and Pharmacogenetics, Division of Clinical Oncology, Department of Internal Medicine, Medical University Graz, Auenbruggerplatz 15, 8036 Graz, Austria.Search for more papers by this authorAbstract
Angiogenesis and cell cycle control play critical roles in breast cancer susceptibility and clinical outcome and are mainly controlled by vascular endothelial growth factor (VEGF) and cyclin-dependent kinases, respectively. Functional germline polymorphisms in these genes alter the function, thereby causing inter-individual differences in breast cancer risk and clinical outcome. In this study, we investigated the influence of the functional polymorphisms VEGF-A rs3025039 C > T and CCND1 rs9344 G > A on risk and clinical outcome in early-stage breast cancer. DNA of 539 female patients with histologically confirmed early-stage breast cancer and 804 control subjects was genotyped for these polymorphisms. Genotypes were tested for associations with breast cancer risk and clinical outcome. There was no significant association between the polymorphisms and breast cancer risk. However, the minor allele of VEGF-A rs3025039 C > T was significantly associated with decreased recurrence-free survival (HR 1.845; 95% confidence interval [CI] 1.035–3.290; P = 0.038) and remained significant in multivariate analysis (HR 1.880; 95% CI 1.020–3.465; P = 0.043). Patients carrying at least one A-allele in CCND1 rs9344 G > A showed a trend towards decreased recurrence-free survival in univariate analysis (HR 2.379; 95% CI 0.841–6.728; P = 0.068). This study provides evidence that the functional VEGF-A rs3025039 C > T polymorphism influences recurrence-free survival in early-stage breast cancer. © 2013 Wiley Periodicals, Inc.
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