Ovarian cancer is the sixth female cancer in western countries and the primary cause of death from cancer in women worldwide Ovarian cancer is about 1.5% during the life of women and the death risk due to ovarian cancer is approximately 1% 1. Described risk factors for the development of ovarian carcinoma include age, obesity, family history of ovarian and other associated malignancies, like breast, uterine and colorectal carcinomas as well as inherited mutations in carcinoma predispositing genes. Various studies also revealed that the risk of ovarian carcinoma might be increased by hormonal and reproductive factors like prolonged consumption of unopposed estrogen replacement therapy, infertility or long–?term use of fertility drugs and low parity or nulliparity. Approximately 10–?15% of invasive ovarian carcinomas are the result of hereditary susceptibility 2,3.
RNAs (lncRNAs) are defined as transcribed RNA molecules that are longer than
200 nucleotides, lack an open reading frame of significant length (<100 amino acids), and have no obvious protein-coding capacity 4,5. LncRNAs were previously believed to be transcriptional noise, but now accumulating evidence suggests that they play important roles in development and differentiation as well as in the proliferation and progress of disease, including cancer. The handful of aberrantly expressed lncRNAs in different cancers suggests that lncRNAs contribute to carcinogenesis, and perform functions in controlling cell cycle progression, apoptosis, invasion, and migration 6. All this convincing evidence supports the idea that the lncRNA and lncRNA SNPs play important roles in the cause of several types of human carcinogenesis, including OC. HOTAIR is a non-coding RNA 2158 nucleotides long located on chromosome 12q13.13; its transcription occurs in the direction opposite to that of the the HOXC genes cluster 7. HOTAIR plays an important role in gene regulation by modifying chromatin structure 7,8. The HOTAIR 5?-domain can recruit the polycomb repressive complex 2 (PRC2), leading to histone H3 lysine 27 trimethylation (H3K27me3) in the HOXD locus, and the HOTAIR 3?-domain connects to the LSD1/CoREST/REST complex with H3 lysine 4 demethylation, coordinately regulating silence of the metastasis suppressor genes 9. Clinically, upregulated expression of HOTAIR is a powerful indicator of poor prognosis for several cancers, including liver cancer 10, esophageal cancer 11, pancreatic cancer 12, breast cancer 13, and gastric cancer 14. A study conducted recently in China comprising 502 BC patients and 504 age-matched healthy controls found that HOTAIR (rs1899663, rs4759314, rs920778) polymorphisms was significantly associated with increased risk of BC 15. It has been reported that HOTAIR rs4759314 and rs7958904 polymorphisms are associated with risk of Epithelial ovarian cancer (EOC) among Chinese women 16. Therefore,in our current study, SNPs (rs1899663, rs4759314) were selected across the whole HOTAIR locus. We investigated the association between HOTAIR tagging SNPs and ovarian cancer risk by molecular epidemiology and case– control study in Iranian Women.