The association of polymorphism within the HOX transcript antisense intergenic RNA (HOTAIR) gene with cholangiocarcinoma in Egyptian patients

Abstract Background Cholangiocarcinoma (CCA) is a rare, aggressive, insidious, and increasingly prevalent cancer characterized by late-stage diagnosis and resistance to chemotherapy. The expression levels of the long non-coding RNA HOTAIR are associated with various pathological processes, including metabolic disorders, autoimmune diseases, and developmental abnormalities. Their involvement in development and progression of multiple malignancies, including CCA, makes them a promising target for therapeutic intervention against this silent killer. Aim To evaluate the association between two single-nucleotide polymorphisms (SNPs), rs4759314 and rs920778 of LncRNA-HOTAIR, and the susceptibility to CCA. Method This cross-sectional study included three groups (totaling 150 participants): 50 patients with cholangiocarcinoma (mean age 55.66 ± 8.92 years; 70% males and 30% females), 50 patients with nonmalignant biliary obstruction (mean age 53.82 ± 8.63 years; 68% males and 32 females), and 50 healthy individuals serving as the control group (mean age 52.20 ± 6.79 years; 54% males and 46% females). The rs4759314 and rs920778 were genotyped using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Clinical data, including CA19.9 levels, were recorded. Result Regarding the clinical characteristics of the cholangiocarcinoma (CCA) patients, our analysis revealed that 82% of cases exhibited focal liver lesions, while 72% presented with lymph node metastasis. Furthermore, the majority of the study population showed normal spleen size (92%) and absence of ascites (56%). Concerning the HOTAIR rs4759314 polymorphism, the AA genotype was the most frequent across all study groups. However, the GG genotype was notably more frequent in the CCA group compared to other study groups. Similarly, the G allele demonstrated a higher frequency in the CCA group than other groups. Statistical analysis indicated that the GG genotype was associated with an increased risk of CCA compared with the AA genotype (OR = 4.18, 95% CI: 1.19–14.60, p = 0.025). Regarding the HOTAIR rs920778 polymorphism, the CT genotype was the most frequent among all groups, with no statistically significant association observed regarding CCA susceptibility. Conclusion The findings suggest that the HOTAIR rs4759314 polymorphism may have a potential association with an increased susceptibility to cholangiocarcinoma, indicating that the G allele could serve as a potential genetic biomarker. Further research is warranted to validate its clinical utility.