Association Between the rs13306703 and rs8192288 Variants of the SOD3 Gene and Breast Cancer and an In Silico Analysis of the Variants’ Impact

<b>Background/Objectives:</b> This study investigated the association between the rs13306703 and rs8192288 variants of the superoxide dismutase 3 (<i>SOD3</i>) gene and breast cancer (BC) in the Mexican population, conducting both genetic and in silico analyses. <b>Methods:</b> 357 healthy women and 386 BC patients were studied using TaqMan assays, qPCR, and RFLP-PCR. <b>Results:</b> The <i>TT</i> genotype and a recessive pattern of these variants were risk factors for BC (<i>p</i> < 0.05). Specifically, the <i>TT</i> genotype of rs13306703 was associated with metastatic lymph nodes, tumor progression (III-IV), luminal A, nonresponse to chemotherapy, and ki-67 ≥ 20% with diabetes mellitus (DM). Meanwhile, the <i>GT</i> genotype of rs8192288 was associated with menopause, luminal A, tumor progression (III-IV), ki-67 ≥ 20%, and a positive estrogen receptor with nonresponse to chemotherapy. Additionally, the <i>TT</i> genotype combined with DM was identified as a BC risk factor (<i>p</i> < 0.05). The <i>TT</i> haplotype was also found to be a risk factor for BC. In silico analysis suggested that these variants might influence <i>SOD3</i> regulation by affecting transcription factors and active enhancer sites. <b>Conclusions:</b> The rs13306703 and rs8192288 variants of the <i>SOD3</i> gene were associated with an increased risk of BC and may alter <i>SOD3</i> regulation through effects on transcription factors, active enhancers, and transcription start sites, with modified motifs in breast epithelium cells.