Background
Long non-coding RNAs (lncRNAs) regulate gene expression and have been implicated in breast cancer (BC) development. Functional polymorphic variants in lncRNA genes may alter their regulatory activity and influence cancer susceptibility. This study aimed to assess the association between selected lncRNA polymorphisms, breast cancer risk, and gene expression levels.

Methods
The study included 100 patients with breast cancer (paired tumor and adjacent normal tissue samples) and 59 women without a history of oncological diseases (control group). The following polymorphic markers were analyzed: SNHG16 rs8038 (G>A), GAS5 rs145204276 (ins/del CAAGG), GAS5 rs55829688 (T>C), MEG3 rs10132552 (T>C), and MEG3 rs7158663 (A>G). Genotyping was performed using real-time PCR. Expression levels of three lncRNAs were evaluated in 20 paired breast cancer samples and 12 control samples.

Results
A significant association was observed between GAS5 rs145204276 and breast cancer risk (OR = 3.88; 95% CI 2.39–6.30; p < 0.0001). The del allele and del/del genotype were identified as risk factors. GAS5 expression was higher in histologically normal breast tissue from patients compared to donors (p < 0.05) and significantly reduced in tumor tissue relative to adjacent normal tissue (p < 0.01). Lower GAS5 expression was observed in ins/ins genotype carriers compared to ins/del + del/del.

MEG3 expression did not differ between controls and normal tissue but was significantly decreased in tumor tissue (p < 0.05). The AA genotype (rs7158663) was associated with reduced MEG3 expression in both normal and tumor tissues.

Conclusions
The del allele of GAS5 rs145204276 and the AA genotype of MEG3 rs7158663 are associated with increased breast cancer risk, likely through reduced lncRNA expression.

The study was supported by the state assignment No. FGFU-2025-0010 of the MS HE of the RF to FSBSI IGPP.