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Polymorphisms of long non-coding RNA HOTAIR and susceptibility to gastrointestinal cancers: A meta-analysis

Xie H, Li Y, Zhao W, Lin Y

Medicine, 2026

Abstract

Background: The long non-coding RNA HOTAIR has been implicated in tumor initiation and progression, and multiple case-control studies have explored whether common HOTAIR single-nucleotide polymorphisms influence susceptibility to gastrointestinal (digestive system) malignancies. However, published findings remain inconsistent across populations and cancer types.

Methods: We systematically searched PubMed, Embase, China National Knowledge Infrastructure, and Wanfang for eligible case-control studies evaluating associations between HOTAIR polymorphisms and digestive system cancer risk. Pooled odds ratios with 95% confidence intervals were calculated to estimate genetic effects. Between-study heterogeneity guided the use of fixed- or random-effects models. Prespecified subgroup analyses, sensitivity analyses, and publication-bias assessments were performed.

Results: A total of 25 studies comprising 12,521 cases and 14,610 controls were included. Overall evidence supported an association between digestive system cancer susceptibility and rs920778 (C>T) as well as rs4759314 (A>G), with signals persisting in several subgroup analyses. In contrast, rs7958904 (G>C) showed a risk-reducing pattern in the overall analysis and in colorectal cancer-focused comparisons. No convincing association was observed for rs1899663 (G>T) or rs874945 (G>A). Evidence for less frequently investigated loci (e.g., rs12826786 and rs17720428) was limited and warrants further validation.

Conclusions:…

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