Abstract
Background and Objectives: Breast cancer is a leading cause of cancer-related deaths globally. This study investigates the impact of genetic polymorphisms in DNA methyltransferases (DNMT1 and DNMT3A) on breast cancer pathomorphology and patient prognosis. Specifically, we focused on DNMT1 polymorphisms rs2228611 and rs2228612 and DNMT3A polymorphisms rs2276598 and rs752208. Materials and Methods: Conducted at the Institute of Oncology of the Lithuanian University of Health Sciences, this study included 201 Lithuanian women with early-stage breast cancer. DNA was extracted from peripheral blood samples, and genotyping for the specified polymorphisms was performed using the PCR-RFLP assay. Statistical analyses were applied to evaluate associations between polymorphisms and clinicopathological characteristics. Results: The non-carriers of the DNMT1 rs2228611 G allele were less likely to be diagnosed at an older age, while the DNMT3A rs752208 T allele was linked to lower-grade tumors. Survival analysis indicated a potential relationship between DNMT3A rs752208 and overall survival, although no significant findings were observed in progression-free or metastasis-free survival. Conclusions: This study suggests that the DNMT1 and DNMT3A polymorphisms may influence breast cancer pathomorphology and prognosis. The DNMT1 rs2228611 G allele may be associated with earlier onset, and the DNMT3A rs752208 T allele might correlate with less aggressive tumors. These findings underscore the potential of DNMT gene polymorphisms as prognostic biomarkers in breast cancer, warranting further investigation with larger sample sizes.