Genetic variants in lncRNA HOTAIR are associated with lung cancer susceptibility in a Chinese Han population in China: a case–control study

Hang Li,1,2 Zitai Yang,1,2 Juan Li,1,2 Xiaoting Lv,1,2 Min Gao,1,2 Yanhong Bi,1,2 Ziwei Zhang,1,2 Shengli Wang,1,2 Sixuan Li,1,2 Na Li,1,2 Zhigang Cui,3 Baosen Zhou,1,2 Zhihua Yin1,2 1Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110001, People’s Republic of China; 2Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang 110001, People’s Republic of China; 3School of Nursing, China Medical University, Shenyang 110122, People’s Republic of China Purpose: 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. Patients and methods: 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. Results: 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. Conclusion: HOTAIR rs4759314 and rs12826786 were associated with lung cancer susceptibility in Chinese Han population. Keywords: lung cancer, lncRNAs, HOTAIR, single nucleotide polymorphism, susceptibility, interactio