Research Article Polymorphisms in Survivin (BIRC5 Gene) Are Associated with Age of Onset in Breast Cancer Patients Ilona Sušac, 1 Petar OzretiT , 2 Maja GregoriT, 3 Mirela LevaIiT Cvok, 2,4 Maja Sabol, 2 Sonja Levanat, 2 Diana Trnski, 2 Domagoj Eljuga, 1,5 Sven Seiwerth, 6,7 Gorana Aralica, 6,8 Mladen Stanec, 5 and Vesna Musani 2 1 Eljuga Polyclinic, 10000 Zagreb, Croatia 2 Division of Molecular Medicine, Ruđer Boˇ skovi´ c Institute, 10000 Zagreb, Croatia 3 Zagreb Health School, 10000 Zagreb, Croatia 4 Kardinal Alojzije Stepinac Kraˇ si´ c Primary School, 10454 Kraˇ si´ c, Croatia 5 Department for Oncoplastic and Reconstructive Surgery, University Hospital for Tumors, 10000 Zagreb, Croatia 6 Institute of Pathology, University of Zagreb School of Medicine, 10000 Zagreb, Croatia 7 Clinical Department of Pathology and Cytology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia 8 Department of Pathology, Clinical Hospital Dubrava, 10000 Zagreb, Croatia Correspondence should be addressed to Vesna Musani; vmusani@irb.hr Received 9 October 2018; Revised 7 June 2019; Accepted 25 June 2019; Published 28 July 2019 Academic Editor: Giandomenico Roviello Copyright © 2019 Ilona Suˇ sac et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Survivin, encoded by BIRC5 gene (baculoviral IAP repeat containing 5), belongs to the family of inhibitors of apoptosis proteins (IAPs). In mammalian cells it participates in the control of mitosis, apoptosis regulation, and cellular stress response. Its expression is increased in almost all types of cancers. Te aim of this study was to investigate the role of BIRC5 polymorphisms in breast cancer (BC) and to connect survivin expression with various clinicopathological characteristics of BC patients. Blood and archival tumour tissue samples were collected from 26 BC patients from Croatia. Survivin expression was determined immunohistochemically. BIRC5 promoter, coding region, and 3’UTR were genotyped. DNA from 74 healthy women was used as control. BIRC5 polymorphisms and survivin expression were tested against age of onset, histological grade, tumour type and size, lymph node status, oestrogen, progesterone, Her2, and Ki67 status. Numbers of samples with weak, moderate, and strong survivin expression were 9 (33.3%), 11 (40.7%), and 7 (25.9%), respectively. Most patients had nuclear survivin staining (92.6%). High survivin expression was signifcantly associated with negative oestrogen receptor status (p=0.007) and positive Ki67 expression (p=0.032). Ki67 expression was also positively correlated with histological grade (p=0.0009). Fourteen polymorphisms were found in BC samples, located mostly in promoter and 3’UTR of BIRC5. Tere was no signifcant diference in the distribution of polymorphisms between BC and control samples. Among clinicopathological characteristics of BC patients, alleles of fve BIRC5 polymorphisms were associated with younger age of onset: c.-644T>C (55.8 years [y] vs. 48.1 y; p=0.006), c.-241C>T (54.2 y vs. 45.0; p=0.029), c.9809T>C (55.8 y vs. 48.1 y; p=0.006), c.-1547C>T (58.3 y vs. 50.9 y; p=0.011), and c.9386T>C (50.8 y vs. 59.5 y; p=0.004). To assess the signifcance of BIRC5 polymorphisms and survivin expression as predictive and prognostic biomarkers for BC further research with a larger sample size is needed. 1. Introduction Breast cancer (BC) is one of the most common malignancies among women worldwide. Despite generally good prognosis for BC patients, there is a wide variation in survival [1]. Some of the common risk factors for BC include age, genetic background, hormonal factors, reproductive and menstrual history, excessive alcohol consumption, radiation, benign breast disease, and obesity [2]. Genetic variation has been shown to afect both susceptibility and prognosis of BC [1]. Genome wide association studies (GWAS) have recently been used to identify new loci for BC, and so far almost Hindawi Journal of Oncology Volume 2019, Article ID 3483192, 10 pages https://doi.org/10.1155/2019/3483192