Single-Nucleotide Polymorphism (SNP) c.73G>A in the UBC9 (E2) SUMO Gene and Breast Cancer Risk in Polish Women

Introduction: Breast cancer is one of the major killers among malignant conditions worldwide, affecting one out of 10 women in industrialized countries and being the leading cause of cancer-related morbidity and mortality in women. The relationships between risk factors and breast cancer development are not exactly known. The selection of the UBC9 gene and its c.73G>A polymorphism (rs11553473) in breast cancer studies is justified by the gene's critical role in sumoylation, its impact on DNA repair, and its association with aggressive tumor characteristics. UBC9 (SUMO-conjugating enzyme) is frequently overexpressed in breast cancer, often 5-8-fold higher than in normal tissues, where it promotes tumor proliferation, invasion, and metastasis, often in a sumoylation-independent manner. Aim: In the present work, the association of polymorphism in the UBC9 genes c.73G>A with breast cancer risk was investigated. Materials and Methods: In the reported study, paraffin-embedded tumor tissue was collected from women with lymph node-negative (n = 59) and lymph node-positive (n = 41) ductal breast carcinoma. Samples from age-matched, cancer-free women (n = 100) served as controls. The genotypes of the UBC9 c.73G>A polymorphism were determined by ASO-PCR methods. Results: In the present work, a significant positive association between the UBC9 c.73G>A G/A genotype and breast cancer is demonstrated. The variant A allele of UBC9 increased breast cancer risk. Some correlation was observed between the genotypes of UBC9 polymorphism and breast cancer invasiveness. A statistically significant increase was observed regarding G/A heterozygote frequency in stage II patients, according to Bloom-Richardson classification. There were no significant differences in genotype distribution among subgroups defined by TNM stage, histological grade, hormone receptor status, or HER-2 expression. Conclusions: In conclusion, the reported study indicates that the polymorphisms of the UBC9 gene may be positively associated with the incidence of breast cancer. However, further research is needed on larger study populations.