A Functional HOTAIR Rs12826786 C > T Polymorphism Is Associated with Breast Cancer Susceptibility and Poor Clinicopathological Characteristics in A Turkish Population: A Hospital-Based Case-Control Study

Abstract

Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is pervasively overexpressed and correlated with tumor invasion, progression, metastasis, and poor prognosis in various human cancers including breast cancer (BC) that plays a role as an oncogenic molecule. A common functional single-nucleotide polymorphism (SNP) (rs12826786 C > T) at the HOTAIR promoter has been reported to influence HOTAIR expression and gastric adenocarcinoma susceptibility, but relation of HOTAIR rs12826786 C > T polymorphism with BC susceptibility and clinicopathological characteristics has yet to be reported. To explore the association of the HOTAIR rs12826786 C > T polymorphism with the risk of BC in a Turkish population, a hospital-based case-control study was carried out consisting of 123 BC patients and 122 age-matched healthy controls. HOTAIR rs12826786 C > T polymorphism was determined by real-time polymerase chain reaction (PCR) using TaqMan assay. We found that women carrying TT genotype of HOTAIR rs12826786 C > T polymorphism had an increased risk of developing BC in both codominant (odds ratio (OR) = 2.24, 95 % confidence interval (CI) 1.05-4.81, P = 0.02) and recessive (OR = 2.49, 95 % CI 1.25-4.97, P = 0.008) inheritance models. Moreover, TT genotype of HOTAIR rs12826786 C > T polymorphism was significantly related with multiple clinicopathological characteristics concerned with worse BC progression such as advanced TNM stage (III and IV), larger tumor size (T3 and T4), and distant metastasis (M1), as well as poor histological grade (III) (P < 0.05). Because of our results put forward for the first time that TT genotype of HOTAIR rs12826786 C > T polymorphism might play crucial roles in genetic susceptibility and poor prognosis for BC in Turkish population, further independent studies are needed to confirm our results in a larger series, as well as in patients of distinct populations.