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

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.

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.

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.

Current pooled data suggest that selected HOTAIR variants - particularly rs920778 and rs4759314 - may contribute to inherited susceptibility to digestive system cancers, whereas rs1899663 and rs874945 appear unrelated in available datasets. Larger, well-designed studies across diverse ancestries and cancer sites are needed to confirm these findings and clarify potential gene-environment interactions.