SNAI1 rs8120550, rs1543442, and rs73113648 polymorphisms and their association with breast cancer phenotype and prognosis

Background and Objectives Breast cancer is a leading cause of cancer-related deaths globally. According to WHO data, in 2022, BC accounted for 6.8% of cancer-related deaths worldwide and 6.2% of such deaths within the Lithuanian population. One of the mechanisms underlying BC is the influence of genetic variants. High-frequency, low-penetrance genetic variants, including single nucleotide polymorphisms (SNPs), are more frequently linked to sporadic breast cancer. The epithelial-to-mesenchymal transition (EMT) is a cellular process that plays a role in embryonic development, wound healing, and tumor formation. EMT is crucial in invasion and subsequent metastasis. Snail1, encoded by the SNAI1 gene, is one of the key factors triggering EMT. In this study, we focused on SNAI1 rs8120550, rs1543442, and rs73113648 polymorphisms and their impact on various pathomorphological features and patients’ prognosis within the Lithuanian breast cancer cohort. Material and Method A total of 199 breast cancer patients were studied. The inclusion criteria were as follows: confirmed diagnosis, early BC stage (I–II), and complete medical documentation. Clinicopathological information was collected from medical records in collaboration with oncologists. Polymorphisms of interest were analyzed with real-time PCR-based genotyping. Statistical analysis was performed using SPSS (31.0.0.0). A pvalue < 0.05 was considered statistically significant. The study received approval from the Kaunas Regional Biomedical Research Ethical Committee (no. BE-2-10, no. P1- BE-2-10/2014,), and written informed consent was obtained from all participants. Results Pearson’s chi‑square analysis revealed significant associations between SNAI1 rs8120550 and disease progression (p = 0.011) and metastasis (p = 0.008). Additionally, rs73113648 was significantly associated with age group (p = 0.041), disease progression (p = 0.002), and metastasis (p = 0.002). In univariate logistic regression analysis, for SNAI1 rs73113648, the TT genotype was significantly associated with older age at diagnosis, showing lower odds compared with the CC genotype (OR = 0.247, p = 0.036). In the analysis of clinical outcomes for rs73113648, the TT genotype was statistically associated with higher odds of progression and metastasis compared with CC genotype (OR = 6.207, p = 0.001; OR = 5.952, p = 0.002, respectively). Rs8120550 demonstrated significant associations with disease progression and metastasis, where the AG genotype was associated with significantly higher odds than the AA genotype (OR = 2.718, p = 0.005; OR = 2.872, p = 0.005, respectively). The following are results after Kaplan-Meier method, which was used to evaluate the association between SNPs and PFS, MFS and OS: rs8120550 showed significant results for PFS (p = 0.012) and for MFS (p = 0.009), while rs73113648 demonstrated statistically significant associations with PFS (p = 0.001) and MFS (p = 0.004). Rs1543442 demonstrated no significant associations with any survival outcomes. In univariate Cox regression analysis, rs8120550 (AG versus AA) were associated with shorter PFS (HR = 2.323, p = 0.006) and MFS (HR = 2.529, p = 0.006), while rs73113648 (TT versus CC) was linked to even shorter PFS (HR = 3.650, p < 0.001) and MFS (HR = 3.567, p = 0.002). Conclusions and Recommendations The study revealed that SNAI1 rs8120550 and rs73113648 were significantly associated with an increased risk of disease progression and metastasis. Both SNPs were also associated with poorer PFS and MFS, with rs73113648 showing the strongest effect. These findings suggest that SNAI1 polymorphisms may have prognostic value for clinical outcomes in early-stage BC, but further studies involving a larger, independent cohort, are recommended to confirm our findings.