Single Nucleotide Polymorphisms in HOTAIR Are Related to Breast Cancer Risk and Prognosis in the Northeastern Chinese Population

Abstract

BackgroundThe long noncoding RNA HOX transcript antisense RNA (HOTAIR) is highly expressed in breast cancer (BC) tissues and is associated with the recurrence and metastasis of BC. Until now, the results of studies on associations between several functional single nucleotide polymorphisms(SNPs) (rs920778, rs1899663, and rs4759314) in HOTAIR with BC susceptibility carried out in different regions of China are still inconsistent. There is no study on correlation between HOTAIR SNPs and prognosis of Chinese population. Therefore, we investigated the relationship between HOTAIR SNPs and susceptibility to and prognosis of BC.MethodWe conducted a population-based case-control study involving 828 BC cases and 905 healthy controls. Peripheral blood DNA was used for genotyping. The association between HOTAIR genotypes and BC risk were estimated by odds ratios (ORs) computed using the binary logistic regression model. The relationships between HOTAIR SNPs and clinicopathological features were tested by Pearson’s chi-square test or Fisher’s exact test. Survival was analyzed using the Kaplan-Meier method.ResultsThe functional rs920778 genetic variant increased BC risk in the codominant model. Individuals with the rs920778 GG genotype had an OR of 2.426 (95% confidence interval [CI] = 1.491–3.947, P < 0.001) for developing BC compared to individuals with the AA genotype. Individuals with the AG genotype had an OR of 1.296 (95% CI = 1.040–1.614, P = 0.021) for developing BC compared to individuals with the AA genotype. Individuals with the rs4759314 GA genotype had a lower BC risk than individuals with the rs4759314 AA/GG genotype (OR = 0.566, 95% CI = 0.398–0.803, P = 0.001). The rs1899663 genotype had no correlation with BC susceptibility. Haplotypes composed of rs920778–rs1899663 and rs920778–rs1899663–rs4759314 could increase BC risk (all P < 0.001). There were no statistically significant associations between HOTAIR SNPs and clinicopathological characteristics. The rs920778 GG/AG genotypes were associated with worse disease-free survival (DFS) (p = 0.012), and the rs4759314 GA genotype was associated with worse DFS and overall survival (OS) (p = 0.011).ConclusionHOTAIR SNPs(rs920778 and rs4759314) are significantly related to BC susceptibility and prognosis in the northeastern Chinese population, indicating the significance in the occurrence and development of BC.

HOTAIR/miR-203/CAV1 Crosstalk Influences Proliferation, Migration, and Invasion in the Breast Cancer Cell

“…A recent study analyzed the in situ expression of HOTAIR in breast cancer patients and showed that a high expression of HOTAIR in tumor tissue is closely related to lymph node metastasis [ 5 ]. A population-based case-control study found that HOTAIR is associated with breast cancer risk and prognosis [ 6 ]. Based on the important role of HOTAIR in breast cancer progression, a recent review summarized the potentially promising therapeutic function of HOTAIR in breast cancer [ 7 ].…”

Genetic Variants of HOTAIR Associated with Colorectal Cancer: A Case-Control Study in the Saudi Population

“…Presently, we reported a strong association of rs920778 G > A with increased CRC risk in the Saudi population, and a potential biomarker, the homozygous mutant genotype “AA”, showed a significant association with the risk of CRC, particularly with gender, age, and location. Some previous studies have reported the association of rs920778 SNP with increased cancer risk in Turkish, Indian, and Chinses populations [ 32 , 34 , 45 ]. Recently, HOTAIR rs920778 polymorphisms with higher survival rates were reported in CRC patients from South Korea [ 19 ] and in breast cancer patients in southeast Iran [ 46 ].…”

“…Wang et al [ 33 ] reported that rs1899663 (G > T) increased lung cancer risk in China, and Hassanzarei et al [ 46 ] reported a negative association of rs1899663 (G > T) with breast cancer in Iran. Additionally, rs1899663 polymorphism is linked with breast cancer risk in Indian and Chinese populations and prostate cancer susceptibility in the Iranian population [ 32 , 34 , 47 ].…”

“…These SNPs were selected on the basis of some recent reports linking them with increased cancer risk. Few molecular epidemiological studies linked HOTAIR rs920778 polymorphism with the risk of breast, cervical, and lung cancer; rs1899663 with lung, breast, and gastric cancer; and rs12816786 with lymphoma [ 31 , 32 , 33 , 34 , 35 ].…”

HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer

“…Single nucleotide polymorphisms (SNPs) are reported to upregulate HOTAIR expression and are correlated with an increased risk of BC. In addition, the GG/AG genotype of rs720778 and GA genotype of rs4759314 are reported to be associated with lower disease-free survival (DFS) and overall survival (OS) and DFS, respectively, in some populations of BC patients [ 83 ]. A similar study in India by Rajagopal et al [ 84 ] reported that a combination of SNPs in NME1 (rs16949649 T > C and rs2302254 C > T) and HOTAIR (e.g., rs920778 C > T and rs1899663 G > T) increased the risk of BC in premenopausal women carrying mutant alleles.…”