Cumulative Evidence for Relationships Between HOTAIR genes and Risk of Cancer and Non-Cancer Disease

Previous genetic studies have documented the presence of single-nucleotide polymorphisms (SNPs) in HOTAIR genes (including rs4759314, rs920778, rs1899663, rs12826786, rs17720428 and rs7958904 polymorphisms) are linked to the risk of multiple diseases. The relationship between polymorphisms in HOTAIR genes and cancer susceptibility has been extensively studied. However, the findings have yielded conflicting results. This article aimed to comprehensively present current knowledge of variants in the HOTAIR genes on the risk of different diseases. Methods: Our methodical search for publications was conducted using Web of Science and Pubmed prior to 17 September 2023. Out of 264 identified publications, 40 were selected for a meta-analysis, utilizing a minimum of two data sources, to investigate whether SNPs in HOTAIR genes play a role in the likelihood of neoplastic and non-neoplastic diseases. Furthermore, a probability test for false positives in reports and Venice's standards was employed to verify the genuineness of the aggregate evidence demonstrating notable links. Results: There was a statistical link between six genetic variations and the risk of developing breast cancer (BC), gastric cancer (GC), cervical cancer, colorectal cancer, lung cancer (LC), psoriasis, and benign prostatic hyperplasia (BPH) (p < 0.05). Among these, six variants, each with four types of cancer and one disease unrelated to cancer, were deemed robust evidence (rs4759314, rs920778 in cervical cancer; rs12826786, rs17720428, rs7958904 and rs1899663 in gastric cancer; rs1899663 in colorectal cancer; rs12826786 in lung cancer and psoriasis). Findings from ENCODE and various public databases indicate that SNPs, backed by solid evidence, could be situated in areas presumed to be functional. Conclusions: The research demonstrated a significant correlation between SNPs in HOTAIR genes and the vulnerability to diverse diseases, shedding light on the crucial role of HOTAIR genes in genetic susceptibility to human illnesses.