Association between long non-coding RNA HOTAIR polymorphism and lung cancer risk: A systematic review and meta-analysis

Abstract

Single nucleotide polymorphism (SNP) of long noncoding RNA (lnc)RNA has been reported to be an important factor in cancer development. Recently, lncRNA homeobox transcript antisense intergenic RNA (HOTAIR) was indicated to induce tumorigenesis of several cancer types, but the association between the SNP of lncRNA HOTAIR and lung cancer susceptibility has remained undetermined. The present meta-analysis aimed to investigate the effect of HOTAIR polymorphism on susceptibility to lung cancer. The PubMed, Ovid Medline, Embase and Cochrane Library databases were thoroughly searched. Studies containing data on the incidence of lung cancer in patients with different HOTAIR SNPs were included. The Hardy-Weinberg equilibrium was analyzed to determine genotype distribution and allele frequencies. The odds ratio (OR) was pooled to evaluate the association of different SNPs with the susceptibility to lung cancer. A total of six studies comprising 1,715 patients with lung cancer and 2,745 healthy controls were finally included. A total of 4 SNPs (rs12826786, rs1899663, rs920778 and rs4759314) were reported. Analyses for all of these SNPs individually indicated that the lncRNA HOTAIR rs1899663 C>A polymorphism was a risk factor for lung cancer (dominant mode, AA+CA vs. CC: OR=0.816, 95% CI=0.707-0.942, P=0.005). The present study was the first meta-analysis investigating the association between lncRNA HOTAIR and lung cancer susceptibility. The results indicated that the lncRNA HOTAIR rs1899663 C>A polymorphism is a risk factor for lung cancer. LncRNA HOTAIR may be of value in lung cancer screening, particularly for populations with high-risk factors, as well as prognosis prediction. Future investigations are required to further clarify the intrinsic mechanism of the role of HOTAIR in the oncogenesis of lung cancer.

Keywords: HOTAIR; SNP; lncRNA; lung cancer; susceptibility.

Figure 1

Flowchart of the literature screening. Records were searched via databases (n=46) and other sources (n=8). Finally, a total of 6 records were considered eligible and included in the present meta-analysis. SNP, single nucleotide polymorphism; lncRNA, long noncoding RNA; HOTAIR, homeobox transcript antisense intergenic RNA.

Figure 2

Sensitivity analysis for each single nucleotide polymorphism. The sensitivity was performed by omitting one study at a time. In each row of the forest plot, one study was omitted. Sensitivity analysis was performed for rs12826786, rs1899663, rs4759314 and rs920778 for all modes including (A) dominant mode, (B) recessive mode, (C) additive mode, (D) heterozygote mode, (E) homozygote mode and (F) allele mode.

Figure 3

Analysis for the rs1899663 C>A polymorphism. (A) The forest plot indicates the pooled OR for the effect of the rs1899663 C>A polymorphism on the risk of lung cancer. (B) Egger's test plot and (C) funnel plot for assessment of publication bias. OR, odds ratio; SND, standard normal distribution; se, standard error.

Figure 4

Subgroup analysis. Subgroup analysis was performed based on (A) Newcastle-Ottawa Scale score quality assessment, (B) type of cancer and (C) P-value of Hardy-Weinberg equilibrium. OR, odds ratio; NSCLC, non-small cell lung cancer.