Polymorphisms in Survivin (BIRC5 Gene) Are Associated with Age of Onset in Breast Cancer Patients

Ilona Sušac; Petar Ozretić; Maja Gregorić; Mirela Levačić Cvok; Maja Sabol; Sonja Levanat; Diana Trnski; Domagoj Eljuga; Sven Seiwerth; Gorana Aralica; Mladen Stanec; Vesna Musani

doi:10.1155/2019/3483192

Polymorphisms in Survivin (BIRC5 Gene) Are Associated with Age of Onset in Breast Cancer Patients

J Oncol. 2019 Jul 28:2019:3483192. doi: 10.1155/2019/3483192. eCollection 2019.

Authors

Ilona Sušac¹, Petar Ozretić², Maja Gregorić³, Mirela Levačić Cvok^{2

4}, Maja Sabol², Sonja Levanat², Diana Trnski², Domagoj Eljuga^{1

5}, Sven Seiwerth^{6

7}, Gorana Aralica^{6

8}, Mladen Stanec⁵, Vesna Musani²

Affiliations

¹ Eljuga Polyclinic, 10000 Zagreb, Croatia.
² Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia.
³ Zagreb Health School, 10000 Zagreb, Croatia.
⁴ Kardinal Alojzije Stepinac Krašić Primary School, 10454 Krašić, 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.

Abstract

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. The 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 significantly 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. There was no significant difference in the distribution of polymorphisms between BC and control samples. Among clinicopathological characteristics of BC patients, alleles of five 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 significance of BIRC5 polymorphisms and survivin expression as predictive and prognostic biomarkers for BC further research with a larger sample size is needed.