Polymorphisms of long non-coding RNA HOTAIR with breast cancer susceptibility and clinical outcomes for a southeast Chinese Han population

Abstract

Hox transcript antisense intergenic RNA (HOTAIR) is a well-known long non-coding RNA (lncRNA) which participates in tumorigenesis and progress of multiple cancers. However, the associations among polymorphisms on HOTAIR, breast cancer (BC) susceptibility and clinical outcomes have remained obscure. In this case-control study, we assessed the interaction between three lncRNA HOTAIR single nucleotide polymorphisms (SNPs) (rs1899663, rs4759314 and rs7958904) on the risk and clinical outcome of breast cancer in a Chinese Han population. In total, 969 breast cancer cases and 970 healthy controls were enrolled in this study. Associations among genotypes, BC risk and survival were evaluated by univariate and multivariate logistic regression to estimate the odds ratio (OR), hazard ratio (HR) and its 95% confidence interval (CI). The disease-free survival (DFS) and overall survival (OS) was calculated by the Kaplan-Meier method. We found that the T allele of rs1899663 and C allele of rs7958904 both achieved significant differences between cases and controls in the single locus analyses (P = 0.017 and 0.010, respectively). Multivariate analyses also revealed the rs1899663 TT genotype and rs7958904 CC genotype were both at higher risk of breast cancer compared with the GG homozygotes (OR = 2.08, 95% CI = 1.20-3.60 and OR = 1.45, 95% CI = 1.01-2.08, respectively). In survival analysis, we observed that the T allele of rs1899663 presented significant differences for both DFS (HR = 1.64, 95% CI = 1.12-2.40) and OS (HR = 2.10, 95% CI = 1.29-3.42) in younger subjects (age ≤ 40). Our findings may provide new insights into the associations among the genetic susceptibility, the fine classifications and the prognosis of breast cancer. Further studies with larger sample size and functional research should also be conducted to validate our findings and better elucidate the underlying biological mechanisms.

Keywords: HOTAIR; breast cancer; genetic susceptibility; polymorphisms; prognosis.

Figure 1. Linkage disequilibrium and genomic location of HOTAIR polymorphisms

Figure 2. Survival curves for rs1899663 and rs4759314 in total patients

(A) Disease free survival of the patients grouped according rs1899663 genotypes. (B) Overall survival of the patients grouped according rs1899663 genotypes. (C) Disease free survival of the patients grouped according rs4759314 genotypes. (D) Overall survival of the patients grouped according rs4759314 genotypes.

Figure 3. Survival curves for rs1899663 in younger patients (age ≤ 40) subgroup

(A) Disease free survival of the younger subjects (age ≤ 40) grouped according rs1899663 genotypes. (B) Overall survival of the younger subjects (age ≤ 40) grouped according rs1899663 genotypes.