Yan Rui, Cao Jingjing, Song Chunhua, Chen Yi, Wu Zhenzhen, Wang Kaijuan, Dai Liping
Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, PR China.
Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, PR China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou 450001, Henan, PR China.
Cancer Epidemiol. 2015 Dec;39(6):978-85. doi: 10.1016/j.canep.2015.10.025. Epub 2015 Nov 9.
Controversial data have emerged on the association between cancer risk and the single-nucleotide polymorphism (SNP, rs920778C>T) in Hox transcript antisense RNA (HOTAIR). No data on the association between HOTAIR polymorphism and breast cancer (BC) susceptibility and reproductive factors have been reported in China. In this study we investigated the association between HOTAIR polymorphisms and BC susceptibility in a population-based case-control study of 502 cases and 504 matched controls in China. Three haplotype tagging SNPs (rs1899663, rs4759314, rs920778) of HOTAIR were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created-restriction-site PCR (CRS-RFLP) assays. False-positive report probability (FPRP) was calculated to test for false-positive associations. Interactions between the SNPs and reproductive factors were further evaluated by the multifactor dimensionality reduction (MDR) method. BC risk reduction was confined to subgroups of age at menarche >14 (OR: 0.42, 95%CI: 0.21, 0.82) and number of pregnancies >2 (OR: 0.65, 95%CI: 0.49, 0.95) for GT+TT rs1899663, and age at menopause ≤ 50 (OR: 0.97, 95%CI: 0.84, 0.99) for AG+GG rs4759314. Subjects with Trs920778 had a significantly increased risk of breast cancer (OR: 1.41, 95%CI: 1.13, 1.75). We observed a significant interaction between rs920778 and reproductive factors, including age at menopause, number of abortions, and family history. Our results were unlikely to be false positives according to FPRP calculation. In conclusion, genetic variant rs920778 in HOTAIR significantly increased the risk of BC, and it may have apparent interaction with reproductive factors in the progression on BC. These findings extend available data on the association between HOTAIR polymorphisms and BC susceptibility.
关于癌症风险与Hox转录反义RNA（HOTAIR）中的单核苷酸多态性（SNP，rs920778C>T）之间的关联，已出现了有争议的数据。在中国，尚未有关于HOTAIR多态性与乳腺癌（BC）易感性及生殖因素之间关联的数据报道。在本研究中，我们在中国一项基于人群的病例对照研究中，对502例病例和504例匹配对照进行了调查，以研究HOTAIR多态性与BC易感性之间的关联。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和创建限制性位点PCR（CRS-RFLP）分析方法，对HOTAIR的三个单倍型标签SNP（rs1899663、rs4759314、rs920778）进行基因分型。计算假阳性报告概率（FPRP）以检验假阳性关联。通过多因素降维（MDR）方法进一步评估SNP与生殖因素之间的相互作用。对于rs1899663的GT+TT基因型，BC风险降低仅限于初潮年龄>14岁的亚组（OR：0.42，95%CI：0.21，0.82）和妊娠次数>2次的亚组（OR：0.65，95%CI：0.49，0.95）；对于rs4759314的AG+GG基因型，BC风险降低仅限于绝经年龄≤50岁的亚组（OR：0.97，95%CI：0.84，0.99）。携带rs920778 T等位基因的受试者患乳腺癌的风险显著增加（OR：1.41，95%CI：1.13，1.75）。我们观察到rs920778与生殖因素之间存在显著相互作用，包括绝经年龄、流产次数和家族史。根据FPRP计算，我们的结果不太可能是假阳性。总之，HOTAIR中的基因变异rs920778显著增加了BC风险，并且在BC进展过程中可能与生殖因素存在明显相互作用。这些发现扩展了关于HOTAIR多态性与BC易感性之间关联的现有数据。
