Genetic variations and interactions of lncRNA HOTAIR and miRNA MIR196A2 on lung cancer risk in a Northeast Chinese population

Lung cancer is the most frequently diagnosed cancer and remains the leading cause of cancer-related death. lncRNA HOTAIR and miRNA MIR196A2 are mainly involved in regulation of gene expression. Single nucleotide polymorphisms (SNP) affecting lncRNA or miRNA sequences may modify their function and influence carcinogenesis. This study aimed to assess the potential of lncRNA HOTAIR and miRNA MIR196A2 SNPs as susceptibility biomarkers associated with lung cancer. Present Northeast-Chinese hospital-based case-control study involved 627 lung cancer cases (442 males and 185 female) and 633 controls (449 males and 184 females). We evaluated association between HOTAIR rs2366152, rs920778 and rs3816153 and MIR196A2 rs11614913 SNPs and lung cancer risk and performed data mining regarding the SNP-SNP and SNP-SNP-smoking duration interactions including HOTAIR , MIR196A2 , PPP1R13L and POLR1G ( PPP1R13L and POLR1G risk SNPs identified in our previous study). No evidence regarding the association between the HOTAIR SNPs and lung cancer risk was found in genetic models of co-dominant, dominant, recessive, over-dominant and log-additive adjusted for smoking-duration. MIR196A2 rs11614913 in the recessive model [adjusted-OR (95% CI) = 0.75 (0.56–0.99), P = 0.038] and the over-dominant model [adjusted-OR (95% CI) = 1.30 (1.04–1.63), P = 0.022] showed associations with lung cancer risk. Haplotype7 (rs2366152 A -rs920778 C -rs3816153 G -rs11614913 T ) was marginally associated with increased risk of lung cancer adjusted for smoking-duration [adjusted-OR (95% CI) = 2.27 (0.98–5.28), P = 0.056]. Multifactor dimensionality reduction (MDR) approach showed that the four best candidate models of interactions selected attributes related to lung cancer risk. MDR analysis also showed smoking-duration or rs11614913 was main effect and synergy interactions between HOTAIR and MIR196A2 or POLR1G rs735482 and smoking-duration were found. In conclusion, present study provides new-evidence that the SNP-SNP interactions and synergy of HOTAIR or HOTAIR - MIR196A2 may associate with lung cancer and smoking-induced lung cancer risk and provides added-evidence that MIR196A2 rs11614913 may associate with lung cancer risk.