ABCB8 Gene Polymorphisms Association with Clinicopathological Properties of Breast Cancer

Background and objectives The ABCB8, a mitochondrial ATP-binding cassette transporter, is critical in regulating iron homeostasis and protecting cells from oxidative stress. Polymorphisms in the ABCB8 gene, including rs17545756 and rs4148844, are likely to affect gene expression and protein functionality, thereby impacting cancer risk. In breast cancer (BC), these variants can affect tumor behavior by modifying mitochondrial function, metabolic pathways, or therapeutic resistance. This study aims to analyze the association of ABCB8 polymorphisms rs17545756 and rs4148844 with BC by evaluating their correlation with tumor phenotype and disease prognosis in BC patients. Understanding these associations may provide insights into the molecular mechanisms of BC progression and support the development of more targeted diagnostic and therapeutic strategies. Material and Method In this study, we analyzed ABCB8 rs4148844 and rs17545756 polymorphisms in 170 patients with BC. Medical information such as age at diagnosis, tumor size, grade, lymph node status, estrogen (ER), progesterone (PR), human epidermal growth factor 2 (HER2) receptor status, metastatic status, disease progression, and death was collected. Genomic DNA was isolated from peripheral blood leukocytes using a commercially available DNA extraction kit (Thermo Fisher Scientific Baltics, Vilnius, Lithuania). The polymorphisms mentioned were assessed using TaqMan (Applied Biosystems Europe BV, UK Branch, Warrington, Cheshire, UK) according to the manufacturer’s instructions on the QuantStudio 3 real-time PCR system (Applied Biosystems, Foster City, CA, USA). The statistical analysis was done with Statistical Package for the Social Sciences (SPSS) 25.0 for Windows. The study was approved by the Kaunas Regional Biomedical Research Ethical Committee (protocol No. 2024- BEC2-137). Results The association between ABCB8 rs17545756 and lymph node involvement was determined (χ2 (2) = 5.479, p = 0.040). Logistic regression analysis revealed that individuals carrying the CT genotype had a significantly higher risk of lymph node metastasis compared to those with the CC genotype (OR = 2.909, 95% CI 1.003–8.439, p = 0.049). Moreover, T allele carriers (vs. non-carriers) had a 3.200-fold increased risk of lymph node metastasis (OR = 3.200, 95% CI 1.121-9.131, p = 0.030). The association between ABCB8 rs17545765 and lymph node metastasis remained statistically significant in a multivariate logistic regression analysis, where factors, such as age at diagnosis, primary tumor size, grade, and receptor status, were included as potential confounding variables. No statistically significant correlations were found between the ABCB8 rs4148844 polymorphism and BC phenotype or prognosis. Conclusions and Recommendations Our findings indicate a significant association between the ABCB8 rs17545756 and lymph node involvement in breast cancer patients. Patients carrying the CT genotype and T allele were at a higher risk of lymph node metastasis, suggesting a potential role of this variant in promoting tumor spread. These results suggest that rs17545756 may serve as a potential genetic marker for metastatic risk in breast cancer.