Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and clinicopathologic features in a Turkish population

Abstract

Overexpression of Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with cancer cell proliferation, invasion, progression, and metastasis as well as poor survival in a variety of human cancers including breast cancer (BC). A common functional single nucleotide polymorphism (SNP) rs920778 (T → C) in the intronic enhancer of the HOTAIR has been reported to influence HOTAIR expression and cancer predisposition, but the association of HOTAIR rs920778 polymorphism with BC susceptibility and clinicopathological features has yet to be investigated. We genotyped HOTAIR rs920778 polymorphism in 245 Turkish women including 123 BC patients and 122 age-matched healthy controls by a real-time polymerase chain reaction (PCR) with the TaqMan assay. We found that the CC genotype of HOTAIR rs920778 polymorphism significantly increased the risk of BC in both codominant (odds ratio (OR) = 2.12, 95 % confidence interval (CI) 1.00-4.51, P = 0.05) and recessive (OR = 2.40, 95 % CI 1.22-4.73, P = 0.01) inheritance genetic models. Our research also indicated an association between the CC genotype of HOTAIR rs920778 polymorphism and clinicopathologic features of tumor, including advanced tumor-node-metastasis (TNM) stage, larger tumor size, distant metastasis, and poor histological grade (P < 0.05). Because our findings suggest for the first time that the CC genotype of HOTAIR rs920778 polymorphism might play important roles in genetic susceptibility to BC development and aggressiveness in a Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different populations.

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

“…Previous studies on the contribution of rs920778 to gastric cancer in a Turkish population [25] also showed no differences between patients and cancer-free controls; however, studies in other tumor types testing the importance of rs920778 or rs12826786 in the Chinese population have shown different allele frequencies between patients and cancer-free controls [22][23][24]. It was also showed previously that rs920778 variants do not influence gastric cancer susceptibility [25], whereas others have showed statistically significant associations between these SNPs and risk to develop gastric cardia adenocarcinoma [22], esophageal squamous cell carcinoma (ESCC) [23], breast cancer [26][27][28] or gastric cancer [24]. Such discrepancies might be attributed to the different genetic backgrounds of the studied populations, different sample sizes, and/or to the variety of tumor types analyzed.…”

“…Although HOTAIR expression has been reported as crucial in the carcinogenic process of many cancer types, and its abnormal expression was associated with patient poor prognosis, tumor grade, growth and invasion, and as a putative therapeutic target in glioma [19][20][21], few studies have focused on the significance of SNPs in HOTAIR affecting cancer risk [22][23][24][25][26][27][28]. Critically, no studies have evaluated the impact of HOTAIR SNPs in glioma risk and patient prognosis.…”

Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

“…reported that the HOTAIR SNP rs7958904 was associated with a low risk of colorectal cancer. Another SNP of HOTAIR, rs920778 (C>T), which increases the risk of developing several cancer types such as breast and gastric cancers [46,47], also appears to be linked to an increased risk for OC and poor prognosis [43]. These SNPs could be used as predictive tools for classifying individuals or populations susceptible to OC.…”

Investigation of the Association of HOTAIR Single Nucleotide Polymorphisms and Risk of Breast Cancer in an Iranian Population

“…Considering the immerse burden of breast cancer and challenges in its screening programs (2), determination of genetic factors which contribute to breast cancer risk among women is of value. In order to find their contribution in breast cancer risk, lncRNAs role in breast cancer has been evaluated in different studies with focus on their differential expression (3) as well as their variants at DNA sequence (4). Hox transcript antisense intergenic RNA (HOTAIR) is among lncRNAs with a defined role in regulation of cancer stem cell (CSC) plasticity and a possible target for anti-CSC treatments (1).…”

“…In the present study, we investigated the association between three single nucleotide polymorphisms (SNPs) in HOTAIR gene (rs12826786, rs1899663 and rs4759314) and breast cancer risk in an Iranian population. The rational for selection of these SNPs was the observed association with breast cancer risk as well as patients' clinicopathological characteristics in other populations (4,13,14).…”