Li Hang, Yang Zitai, Li Juan, Lv Xiaoting, Gao Min, Bi Yanhong, Zhang Ziwei, Wang Shengli, Li Sixuan, Li Na, Cui Zhigang, Zhou Baosen, Yin Zhihua
Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110001, People's Republic of China,
Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang 110001, People's Republic of China,
Cancer Manag Res. 2018 Oct 31;10:5209-5218. doi: 10.2147/CMAR.S175961. eCollection 2018.
HOX transcript antisense RNA (HOTAIR) plays important roles in carcinogenesis of various kinds of malignant tumors, including lung cancer. Single nucleotide polymorphisms (SNPs) in HOTAIR were reported to be associated with susceptibility of several kinds of cancers. The present study assessed the associations between three SNPs (rs4759314, rs12826786, and rs920778) and lung cancer susceptibility, as well as gene-environment interaction between smoking exposure and the polymorphisms.
A case-control study including 551 patients and 543 healthy controls was performed. The associations between SNPs and lung cancer susceptibility were assessed by logistic regression model.
rs4759314 was observed to increase the susceptibility of lung cancer, lung adenocarcinoma, squamous lung cancer, and small cell lung cancer statistically significantly (OR of 4.048 for lung cancer; 3.584 for lung adenocarcinoma; 4.671 for squamous lung cancer; 4.502 for small cell lung cancer). In stratified analysis for sex and smoking exposure, rs4759314 GG and AG genotype was also observed to increase the risk of lung cancer statistically significantly (OR of 5.221 for male; 3.491 for female; 3.653 for nonsmoking individuals; 4.458 for smoking individuals). Results of gene-environment interaction analysis showed that there was no interaction between smoking exposure and rs4759314 on additive scale. Results of logistic regression model suggested that the interaction between smoking and rs4759314 was statistically significant on multiplicative scale. rs12826786 CT genotype carriers and T allele could decrease the risk of developing lung cancer (OR of 0.751 for CT carriers; 0.785 for T allele), and in dominant model, TC and TT genotype carriers also have a 0.249-fold decrease risk compared with CC genotype carriers. In stratified analysis for smoking exposure, TC and TT have a 0.432-fold decreased risk compared with CC genotype carriers.
HOTAIR rs4759314 and rs12826786 were associated with lung cancer susceptibility in Chinese Han population.
HOX转录本反义RNA（HOTAIR）在包括肺癌在内的多种恶性肿瘤的致癌过程中发挥重要作用。据报道，HOTAIR中的单核苷酸多态性（SNP）与几种癌症的易感性相关。本研究评估了三个SNP（rs4759314、rs12826786和rs920778）与肺癌易感性之间的关联，以及吸烟暴露与这些多态性之间的基因-环境相互作用。
进行了一项病例对照研究，包括551例患者和543例健康对照。通过逻辑回归模型评估SNP与肺癌易感性之间的关联。
观察到rs4759314在统计学上显著增加了肺癌、肺腺癌、肺鳞癌和小细胞肺癌的易感性（肺癌的OR为4.048；肺腺癌为3.584；肺鳞癌为4.671；小细胞肺癌为4.502）。在按性别和吸烟暴露进行的分层分析中，还观察到rs4759314的GG和AG基因型在统计学上显著增加了肺癌风险（男性的OR为5.221；女性为3.491；非吸烟个体为3.653；吸烟个体为4.458）。基因-环境相互作用分析结果表明，吸烟暴露与rs4759314在相加尺度上没有相互作用。逻辑回归模型结果表明，吸烟与rs4759314之间的相互作用在相乘尺度上具有统计学意义。rs12826786的CT基因型携带者和T等位基因可降低患肺癌的风险（CT携带者的OR为0.751；T等位基因为0.785），在显性模型中，TC和TT基因型携带者与CC基因型携带者相比，风险也降低了0.249倍。在按吸烟暴露进行的分层分析中，与CC基因型携带者相比，TC和TT的风险降低了0.432倍。
HOTAIR rs4759314和rs12826786与中国汉族人群的肺癌易感性相关。
