Abstract
Cancer ranks as the second leading cause of mortality worldwide, prompting extensive investigations into factors contributing to its development. Among these factors, genetic variations, known as genotypic polymorphisms, have been identified as significant influencers in the susceptibility to various types of cancer. Recent research has focused on exploring the connection between polymorphisms in the Long Non-coding RNA HOTAIR and cancer risk. However, the results from these studies have been inconsistent, leading to ambiguity and controversy. To address this uncertainty, we conducted a systematic analysis by gathering relevant studies from PubMed, EMBASE, and Google Scholar. Specifically, we focused on three well-studied polymorphisms within the HOTAIR lncRNA (HOTAIR rs920778 C > T, HOTAIR rs1899663 G > T, HOTAIR rs4759314 A > G) and their association with cancer risk. Our meta-analysis included data from 48 case-control studies involving 42,321 cases and 54,137 controls. The results of our updated meta-analysis revealed a significant correlation between HOTAIR rs1899663 G > T and HOTAIR rs4759314 A > G polymorphisms and overall cancer risk, particularly in the homozygous and recessive genetic models. Subgroup analysis further revealed that these associations were notably pronounced in the Asian population but not observed in the Iranian population. Furthermore, our findings underscore the potential of HOTAIR polymorphisms as diagnostic markers for overall cancer risk, particularly in gynecological cancers, precisely, HOTAIR rs1899663 G > T polymorphism in breast cancer. In conclusion, our systematic analysis provides compelling evidence that Long Non-coding RNA HOTAIR polymorphisms are linked to cancer risk, particularly in certain populations and cancer types, suggesting their potential clinical relevance as diagnostic indicators.