Jian Zhang, Xu Liu, Liang-Hao You, Rui-Zhi Zhou

HOTAIR, a well-known long non-coding RNA, is involved in carcinogenesis and progression of multiple cancers. Molecular epidemiological studies suggest that HOTAIR polymorphisms may be associated with cancer susceptibility, but the results remain controversial. To derive a more precise evaluation, we performed a meta-analysis focused on the associations between HOTAIR polymorphisms and cancer risk for the first time. PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence interval (CI) were applied to assess the association between HOTAIR rs920778 C>T, rs4759314 A>G, rs7958904 G>C, and rs1899663 G>T polymorphisms and cancer susceptibility. Analyses were conducted to detect heterogeneity, sensitivity, and publication bias in order to measure the robustness of our findings. Overall, 13 related studies involving 7,151 patients and 8,740 control samples were analyzed. Significant associations between the HOTAIR rs920778 polymorphism and cancer risk were observed (T vs C: OR =1.33, 95% CI =1.17-1.53; TT vs TC + CC: OR =1.55, 95% CI =1.21-2.00; TC + TT vs CC: OR =1.33, 95% CI =1.11-1.59; TT vs CC: OR =2.02, 95% CI =1.31-3.10) in the total population, as well as in subgroup analyses. For rs4759314 A>G polymorphism, a similarly increased risk was found in the gastric cancer group. However, significant decreases in cancer risk were observed both in the overall population and colorectal cancer group for rs7958904 G>C polymorphism. In addition, no significant association was detected between rs1899663 G>T polymorphism and cancer susceptibility. In conclusion, our meta-analyses suggest that HOTAIR polymorphisms may be associated with the risk of cancer development.