3 Kaplan Meier plots for overall survival and recurrence free interval. concentrations, but not to GPX3 activity, supporting a negative role of SELENOP-aAb on Se transport. SELENOP-aAb were associated with age, but impartial of tumor characteristics. After fully adjusting for potential confounders, SELENOP-aAb were associated with higher recurrence, HR(95%CI)?=?1.87(1.17C2.99), particularly in patients with low Se concentrations, HR(95%CI)?=?2.16(1.20C3.88). Associations of SELENOP-aAb with recurrence and mortality were linear and dose-dependent, with fully adjusted HR(95%CI) per log increase of 1 1.25(1.01C1.55) and 1.31(1.13C1.51), respectively. Conclusion Our results indicate a prognostic and pathophysiological relevance of SELENOP-aAb in breast malignancy, with potential relevance for other malignancies. Assessment of SELENOP-aAb at time of diagnosis identifies patients with a distinctly elevated risk for a poor prognosis, impartial of established prognostic factors, who may respond favourably to Se supplementation. strong class=”kwd-title” Keywords: SELENOP, Glutathione peroxidase, Selenium, Prognosis, Cohort study Graphical abstract Open in a separate windows Abbreviations BIbinding indexCIconfidence intervalCVcoefficient of variationERoestrogen receptorGPX3glutathione peroxidaseHER2human epidermal growth factor receptorHRhazard ratioIQRinterquartile rangeKi67Kiel-antigen nr. 67NHGNottingham Histological GradeNKBCSwedish Clodronate disodium National Quality Registry for Breast CancerOSoverall survivalPGRprogesterone receptorPMMpredictive mean matchingRCSrestricted cubic splineRFIrecurrence free intervalRLUrelative light unitsSCAN-BSwedish Cancerome Analysis Network C BreastSEAPsecreted alkaline phosphataseSELENOPselenoprotein PSELENOP-aAbselenoprotein P autoantibodiesSeSeleniumTXRFtotal x-ray fluorescence 1.?Introduction Breast cancer accounts for one quarter of all cancers, and one sixth of all cancer deaths in women [1]. Given the high incidence, most effort for reducing mortality over recent years has been put on early detection with screening programs [2,3]. However, the established prognostic factors including mainly tumor characteristics (histological grade, receptor expression) and tumor stage remained widely unchanged. Discovery of additional factors for Clodronate disodium the early identification of patients at high risk for breast malignancy recurrence and subsequent intensified adjuvant therapy may improve prognosis. The trace element Clodronate disodium selenium (Se) is essential for life, owing to its effects executed as active constituent of selenoproteins [4,5]. Mainly due to the function of several of the selenoproteins controlling redox status, antioxidative reactions and protective pathways, a beneficial role of Se for maintaining health and avoiding disease has been discussed since more than 40 years [6,7]. While no consistent results were obtained for cancer incidence [[8], [9], [10]], several independent studies reported dose-dependent Clodronate disodium associations of low Se status with poor prognosis. An inverse association of Se status with cancer-prognosis is usually explained for multiple malignancy sites, including laryngeal [11], colorectal [12,13], lung [13,14], prostate [13], skin [15], and breast [[16], [17], [18], [19], [20]], and it was also observed in large-scale studies assessing all-cancer mortality including NHNAES III [13]. Most of the studies that analysed prognosis of patients with breast malignancy by Se used blood sampling to determine Se concentrations in serum or plasma. In our recent study, the association with prognosis was assessed using three different serum biomarkers, namely total Se, the Se transport protein selenoprotein P (SELENOP), and the enzymatic activity of extracellular Se-dependent glutathione peroxidase (GPX3). All three biomarkers were inversely associated with prognosis. Besides these interrelated biomarkers of Se status, natural autoantibodies to SELENOP (SELENOP-aAb) have recently been reported in healthy subjects and thyroid patients, obviously capable of interfering with regular Se transport by SELENOP [21]. The aim of the study was to Clodronate disodium assess the prognostic value of SELENOP-aAb in a large multicentre population-based cohort of newly diagnosed breast malignancy patients. 2.?Methods 2.1. Study populace Since August 30th 2010, the multicentric prospective Sweden Cancerome Analysis Network C Breast (SCAN-B) study (ClinicalTrials.gov ID “type”:”clinical-trial”,”attrs”:”text”:”NCT02306096″,”term_id”:”NCT02306096″NCT02306096) enrols patients with a new diagnosis of primary invasive breast Rabbit Polyclonal to RBM5 malignancy systematically, with the aim of identifying novel genomic and serum prognostic factors [16,22,23]. With multiple participating hospitals in Sweden in Malm?, Lund, Helsingborg, Kristianstad, V?xj?, Halmstad, Uppsala, Karlskrona, Varberg, and Ljungby, SCAN-B included almost 85% of all cases in the catchment region since its initiation [22]. Patients with a pre-surgical diagnosis or suspicion of main invasive breast malignancy were eligible. Among this group, patients with a previous history of contralateral breast cancer, without planned treatment, without planned treatment in any of the participating hospitals, with an unclear treatment status or with a generalized disease state at time of diagnosis, i.e. with distant metastases, were excluded. A total of 5417 patients meeting the eligibility and exclusion criteria were registered between September 1st 2010 and March 31st 2015. For the purpose of our study, we aimed to include 2000 patients. Hence, the first 2903 consecutive cases were selected. After excluding 915 cases, mainly due to missing serum, samples of 1988 female patients were finally included in the current analyses (Supplementary Fig. 1). 2.2. Follow up and endpoint retrieval.