Association of long non-coding RNA HOTAIR polymorphisms with colorectal cancer: a meta-analysis

Several studies have identified that HOTAIR polymorphisms were expressed abnormally in a range of cancers, including breast, gastric, liver, and lung cancers. However, the impact of this gene on colorectal cancer (CRC) remains a topic of debate. To obtain the most accurate results, the association of HOTAIR polymorphisms with CRC risk was analyzed in this meta-analysis (MA). The PubMed, Embase, Cochrane, and Web of Science databases were searched to find the correlation of HOTAIR polymorphisms with CRC up to February 2024. The association of HOTAIR polymorphisms with CRC susceptibility was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Five relevant studies were identified in total. In all HOTAIR polymorphism studies involving CRC, it was found that the subgroup analysis by ethnicity revealed that the rs1899663 G > T codominant and dominant models were positively correlated with CRC development in Asian populations and negatively correlated with CRC development in non-Asian populations (Codominant: OR = 0.70, 95% CI = 0.39–1.25; D: Dominant: OR = 0.65, 95% CI = 0.28–1.53). This MA indicates that HOTAIR polymorphism-the rs1899663 G > T genotype-might have a racially specific impact on CRC risk. This meta-analysis is the first to demonstrate a “race-reversed” effect of HOTAIR rs1899663 on colorectal cancer risk, providing pivotal evidence for race-stratified screening, polygenic risk score calibration, and patient selection in HOTAIR-targeted therapies within the framework of precision medicine. This meta-analysis is the first to demonstrate a “race-reversed” effect of HOTAIR rs1899663 on colorectal cancer risk, providing pivotal evidence for race-stratified screening, polygenic risk score calibration, and patient selection in HOTAIR-targeted therapies within the framework of precision medicine.

多项研究已证实，长链非编码RNA HOTAIR的多态性在多种癌症中存在异常表达，涵盖乳腺癌、胃癌、肝癌与肺癌。然而，该基因对结直肠癌（colorectal cancer, CRC）的影响仍存在争议。为获得最精准的研究结果，本项荟萃分析（meta-analysis, MA）针对HOTAIR多态性与CRC患病风险的相关性展开了分析。本研究检索了PubMed、Embase、Cochrane及Web of Science数据库，截至2024年2月，共纳入探讨HOTAIR多态性与CRC相关性的相关文献。本研究采用比值比（odds ratios, ORs）与95%置信区间（confidence intervals, CIs）评估HOTAIR多态性与CRC易感性的关联。最终共纳入5项相关研究。在所有纳入的CRC相关HOTAIR多态性研究中，按种族进行的亚组分析结果显示，rs1899663 G>T的共显性模型与显性模型在亚洲人群中与CRC发生呈正相关，而在非亚洲人群中则呈负相关（共显性模型：OR=0.70，95%CI=0.39~1.25；显性模型：OR=0.65，95%CI=0.28~1.53）。本项荟萃分析表明，HOTAIR多态性——即rs1899663 G>T基因型——对CRC患病风险的影响可能存在种族特异性。本项荟萃分析首次证实了HOTAIR rs1899663对CRC患病风险存在"种族反转"效应，为精准医学框架下的种族分层筛查、多基因风险评分校准以及HOTAIR靶向治疗的患者筛选提供了关键证据。本项荟萃分析首次证实了HOTAIR rs1899663对CRC患病风险存在"种族反转"效应，为精准医学框架下的种族分层筛查、多基因风险评分校准以及HOTAIR靶向治疗的患者筛选提供了关键证据。