Balkan Journal of Medical Genetics

ASSOCIATION OF E-SELECTIN S128R POLYMORPHISM WITH HEREDITARY BREAST CARCINOMA SUSCEPTIBILITY IN TURKISH PATIENTS WITHOUT BRCA1/2 GERMLINE MUTATIONS
Yararbas K, Atalay PB
*Corresponding Author: Kanay Yararbas, M.D., Assistant Professor, Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University Faculty of Medicine; İçerenköy Mahallesi, Kayisdagi Caddesi, No: 32, 34742, Istanbul, Turkey. Tel: +90-216-500-4785. Fax: +90-216-500-5076. E-mail: kanay.yararbas@ acibadem.edu.tr
page: 27

INTRODUCTION

Breast cancer is one of the most common invasive cancers in the female population worldwide and in Turkey [1]. Breast cancer is a multifactorial disease driven by both genetic and non genetic etiological factors. Non genetic environmental factors such as pregnancy, hormone replacement therapies, obesity and alcohol consumption are known to be closely linked to breast cancer risk [2]. The well-characterized hereditary form of breast cancer is caused by germline pathogenic variants in BRCA1/2 [3]. Early studies conducted on selected multiple-case families have estimated that approximately 80.0% of BRCA1/2 mutation carriers would develop breast cancer by age 70 [4,5]. However, in a later meta-analysis study that pooled the data of studies including patients unselected for family history, it was reported that the observed risk for breast cancer development in BRCA1 and BRCA2 mutation carriers by age 70 was 65.0 and 45.0%, respectively, which were lower than the estimated value [6,7]. Additionally, individuals of high-risk families who do not carry BRCA1/2 mutations are also at an increased risk for developing breast cancer [4,7]. All these data strongly suggest that other than the well-studied BRCA1/2 genes, additional genetic factors are also involved in a predisposition to breast cancer. However, not much is known about the genes contributing to breast cancer susceptibility in non carriers of the BRCA1/2 mutations. Selectins are adhesion molecules, which are expressed by endothelial cells, thrombocytes and leukocytes, and have three subsets, namely L-, P- and E-selectins [8]. Structurally, selectins contain an N-terminal, calciumdependent lectin domain, an epidermal growth factor-like domain, regulatory elements, a transmembrane domain, and a short cytoplasmic tail [9]. Intracellular and extracellular interactions mediated by adhesion molecules are critical for the dissemination of metastatic tumor cells. Loss of cell-cell and/or cell-matrix adhesions allows malignant tumor cells to escape from their primary micro environment and to acquire a more motile and invasive phenotype, and thereby enables them to migrate to the other sides of the body. Consistent with this, E-selectin is involved in migration and metastasis [8,10-18] that are two critical steps in carcinogenesis. E-selectin is a cell surface glycoprotein expressed on endothelial cells after activation by cytokines. Several studies have demonstrated that serum E-selectin levels are elevated in patients with a variety of cancers, including ovarian, breast and gastric cancers [14]. Numerous single nucleotide polymorphisms (SNPs) of the E-selectin gene have been identified, among which the most common variant is the g.7161A/C or A561C missense variant (rs5361) leading to a serine to arginine substitution in exon 4 at position 128 (S128R) (NG_012124.1:g.7161A>C, NM_000450.2: c.445A>C, NP_000441.2: p.Ser149Arg) [19]. The E-selectin S128R (A/C) polymorphism alters the binding specificity of the extracellular domain and thus facilitates ligand binding, which in turn improves the adhesion of lymphoid and myeloid cells to the endothelium [20-22]. In the E-selectin gene variants, the S128R polymorphism is of particular interest as it is clinically associated with increased cancer risk [23]. The present study aimed to investigate whether the S128R polymorphism of the E-selectin gene contributes to development of breast cancer in patients with breast cancer but without BRCA1/2 mutations in the Turkish population. To the best of our knowledge, this study is the first to investigate the correlation between the S128R polymorphism and breast cancer in the absence of BRCA1/2 mutations in the Turkish population.

Number 27 VOL. 27 (1), 2024	Number 26 Number 26 VOL. 26(2), 2023 All in one
Number 26 VOL. 26(2), 2023	Number 26 VOL. 26, 2023 Supplement
Number 26 VOL. 26(1), 2023	Number 25 VOL. 25(2), 2022
Number 25 VOL. 25 (1), 2022	Number 24 VOL. 24(2), 2021
Number 24 VOL. 24(1), 2021	Number 23 VOL. 23(2), 2020
Number 22 VOL. 22(2), 2019	Number 22 VOL. 22(1), 2019
Number 22 VOL. 22, 2019 Supplement	Number 21 VOL. 21(2), 2018
Number 21 VOL. 21 (1), 2018	Number 21 VOL. 21, 2018 Supplement
Number 20 VOL. 20 (2), 2017	Number 20 VOL. 20 (1), 2017
Number 19 VOL. 19 (2), 2016	Number 19 VOL. 19 (1), 2016
Number 18 VOL. 18 (2), 2015	Number 18 VOL. 18 (1), 2015
Number 17 VOL. 17 (2), 2014	Number 17 VOL. 17 (1), 2014
Number 16 VOL. 16 (2), 2013	Number 16 VOL. 16 (1), 2013
Number 15 VOL. 15 (2), 2012	Number 15 VOL. 15, 2012 Supplement
Number 15 Vol. 15 (1), 2012	Number 14 14 - Vol. 14 (2), 2011
Number 14 The 9th Balkan Congress of Medical Genetics	Number 14 14 - Vol. 14 (1), 2011
Number 13 Vol. 13 (2), 2010	Number 13 Vol.13 (1), 2010
Number 12 Vol.12 (2), 2009	Number 12 Vol.12 (1), 2009
Number 11 Vol.11 (2),2008	Number 11 Vol.11 (1),2008
Number 10 Vol.10 (2), 2007	Number 10 10 (1),2007
Number 9 1&2, 2006	Number 9 3&4, 2006
Number 8 1&2, 2005	Number 8 3&4, 2004
Number 7 1&2, 2004	Number 6 3&4, 2003
Number 6 1&2, 2003	Number 5 3&4, 2002
Number 5 1&2, 2002	Number 4 Vol.3 (4), 2000
Number 4 Vol.2 (4), 1999	Number 4 Vol.1 (4), 1998
Number 4 3&4, 2001	Number 4 1&2, 2001
Number 3 Vol.3 (3), 2000	Number 3 Vol.2 (3), 1999
Number 3 Vol.1 (3), 1998	Number 2 Vol.3(2), 2000
Number 2 Vol.1 (2), 1998	Number 2 Vol.2 (2), 1999
Number 1 Vol.3 (1), 2000	Number 1 Vol.2 (1), 1999
Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact