Emerging LncRNA HOTAIR and NME1 polymorphisms in ovarian cancer risk: A pilot case-control study in South Indian...

Long non-coding RNAs (lncRNAs) are increasingly recognized as clinically relevant regulators of cancer susceptibility, progression, and therapeutic response. However, the contribution of low-penetrance genetic variants affecting lncRNAs and metastasis suppressor genes to ovarian cancer (OC) risk remains incompletely defined. In this population-based case-control study, we evaluated the genetic and clinical relevance of polymorphisms in HOTAIR (rs1899663, rs920778) and NME1 (rs2302254, rs16949649) in South Indian women for the first time.

A total of 494 subjects (240 OC patients and 254 age-matched controls) were enrolled. Genomic DNA was isolated from peripheral whole blood, and genotyping was performed using the PCR-RFLP method. Logistic regression models were applied to estimate OC risk, while linkage disequilibrium (LD), haplotype, and clinicopathological correlation analyses were conducted to assess combined genetic effects on the disease susceptibility.

Both HOTAIR variants showed significant associations with increased OC susceptibility. Carriers of the rs1899663 G/T and T/T genotypes exhibited 2.88- and 2.23-fold elevated risk, respectively (p < 0.001), while the rs920778 C/C genotype conferred a 2.24-fold increased risk (p = 0.006). NME1 rs2302254 was also strongly associated with OC risk, particularly the T/T genotype (OR = 3.79; p < 0.0001), whereas rs16949649 showed no significant effect. Clinically, rs920778 correlated with tumor stage and age at onset, and rs2302254 was associated with advanced disease stage. Gene-specific haplotype analysis revealed significant associations for HOTAIR (T-C and T-T) and NME1 (T-T and C-T) haplotypes with OC risk (global p < 0.001), although LD between variants within each locus was weak, suggesting largely independent allelic contributions.

Overall, these findings suggest that HOTAIR and NME1 polymorphisms may contribute to genetic susceptibility in OC and warrant further investigation and functional validation in larger, well-characterized cohorts for their potential utility as biomarkers for risk stratification.