Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, PR China.
Department of Biological Sciences, The University of Texas at El Paso, TX, 79968, USA.
Sci Rep. 2018 Mar 16;8(1):4680. doi: 10.1038/s41598-018-22881-x.
Functional polymorphisms in Linc-ROR may change its ability of regulation by regulating Linc-ROR expression. However, these functional polymorphisms in Linc-ROR and their associations with breast cancer (BC) susceptibility were scarcely reported. In this molecular epidemiological study, four SNPs (rs6420545, rs4801078, rs1942348 and rs9636089) were selected in Linc-ROR by bioinformatics method. Unconditional logistic regression model was performed to analyze the associations between four SNPs and BC susceptibility adjusted for reproductive factors. Quantitative real-time (qRT) PCR was used to evaluate relative expression of Linc-ROR in plasma. The interactions of gene reproductive factors were assessed by Multifactor Dimensionality Reduction (MDR) method. A novel finding showed TT (OR: 1.79; 95%CI: 1.20-2.68) genotype of rs4801078 in Linc-ROR had a significant association with the higher risk of BC and the expression of Linc-ROR mRNA was closely related with the alleles of rs4801078. In addition, we found the interaction of rs4801078, number of pregnancy and menopausal status might increase BC risk (OR: 2.78; 95%CI: 2.74-3.61). Our results suggest that interactions of SNPs in Linc-ROR and reproductive factors might contribute to BC risk, and alleles of rs4801078 might affect Linc-ROR expression level.
功能性 Linc-ROR 多态性可能通过调节 Linc-ROR 的表达来改变其调节能力。然而，Linc-ROR 中的这些功能性多态性及其与乳腺癌（BC）易感性的关系尚未得到充分报道。在这项分子流行病学研究中，通过生物信息学方法在 Linc-ROR 中选择了四个 SNPs（rs6420545、rs4801078、rs1942348 和 rs9636089）。采用条件逻辑回归模型调整生殖因素后分析四个 SNP 与 BC 易感性的关系。采用定量实时（qRT）PCR 评估血浆中 Linc-ROR 的相对表达。采用多因素降维（MDR）方法评估基因-生殖因素的相互作用。一项新发现表明，Linc-ROR 中 rs4801078 的 TT（OR：1.79；95%CI：1.20-2.68）基因型与 BC 的高风险显著相关，并且 Linc-ROR mRNA 的表达与 rs4801078 的等位基因密切相关。此外，我们发现 rs4801078、妊娠次数和绝经状态的相互作用可能会增加 BC 风险（OR：2.78；95%CI：2.74-3.61）。我们的研究结果表明，Linc-ROR 中 SNP 与生殖因素的相互作用可能导致 BC 风险增加，并且 rs4801078 的等位基因可能影响 Linc-ROR 的表达水平。
