Comprehensive investigation of long non-coding RNA HOTAIR polymorphisms and cancer risk - A current meta-analysis encompassing 96,458 participants

Sep 21, 2026

Uploaded by Riley

Cancer remains a major cause of mortality globally, with evidence linking inherited genetic polymorphisms to susceptibility across many cancer types. This meta-analysis systematically compiles case–control studies from PubMed, EMBASE, and Google Scholar, focusing on three HOTAIR lncRNA variants (rs920778 C>T, rs1899663 G>T, rs4759314 A>G). Results show significant associations for rs1899663 G>T and rs4759314 A>G with overall cancer risk, especially under homozygous and recessive models, with effects strongest in Asian populations. Findings also support HOTAIR polymorphisms as potential diagnostic markers, particularly for gynecological cancers such as breast cancer.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Background and rationale

Genetic polymorphisms and SNPs in cancer

lncRNA biology and the role of HOTAIR

Prior findings and need for clarification

Study design and data sources

Search strategy and study selection

Focus variants within HOTAIR

Meta-analysis results

Overall cancer risk associations

Genetic models

Subgroup findings by population and cancer type

Clinical implications and conclusions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Comprehensive investigation of long non‑coding RNA HOTAIR polymorphisms and cancer risk: a current meta‑analysis encompassing 96,458 participants B. Madhu Krishna1, Pankaj Garg2, Sravani Ramisetty1, Ayalur Raghu Subbalakshmi1, Prakash Kulkarni2, Ravi Salgia1 & Sharad S. Singhal1* 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 polymorphismsas 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. Keywords Long non-coding RNA (lncRNA), HOX transcript antisense intergenic RNA (HOTAIR), Single nucleotide polymorphisms (SNPs), Gynecological cancer Abbreviations CI HOTAIR lncRNA ORs SNPs Confidence interval HOX transcript antisense intergenic RNA Long non-coding RNA Odds ratio Single nucleotide polymorphisms 1Department of Medical Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA 91010, USA. 2Department of Chemistry, GLA University, Mathura, Uttar Pradesh 281406, India.* email: [ssinghal@coh.org](ssinghal@coh.org) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) Cancer is a prominent contributor to mortality rates in the United States, as indicated by recent data forecasting 2,001,140 new cases and 611,720 deaths from cancer in the US alone by 20241. The escalating number of cancer patients annually in both developed and developing nations underscores the perplexing nature of the molecular pathways leading to malignancies2–4. Various factors such as smoking, adiposity, infectious agents, and alcohol abuse have been linked to the susceptibility, onset, and fatality of cancer. Investigations have unveiled the oncogenic potential of diverse genetic variations, prompting heightened scrutiny as potential risk determinants5,6. Among these, single nucleotide polymorphisms (SNPs) are prevalent genetic elements associated with multiple cancer forms7–9. Long non-coding RNA (lncRNA) constitutes a category of RNA molecules exceeding 200 nucleotides in length and were previously disregarded due to their lack of protein-coding capability10–12. Recent breakthroughs, however, have elucidated the pivotal role of lncRNAs play in the modula

FAQs

Which HOTAIR polymorphisms were evaluated for cancer risk?

The meta-analysis focused on HOTAIR rs920778 C>T, rs1899663 G>T, and rs4759314 A>G variants.

What did the pooled results show about overall cancer risk?

Significant correlations were found for rs1899663 G>T and rs4759314 A>G with overall cancer risk, particularly in homozygous and recessive genetic models.

Do the associations differ by population or cancer type?

Subgroup analysis indicated stronger associations in Asian populations, while results were not observed in the Iranian population. The findings also emphasized potential diagnostic relevance for gynecological cancers, including breast cancer.

Sep 21, 2026

Uploaded by Riley