Gallegos-Arreola Martha Patricia, Garibaldi-Ríos Asbiel Felipe, Magaña-Torres María Teresa, Figuera Luis E, Gómez-Meda Belinda Claudia, Zúñiga-González Guillermo Moisés, Puebla-Pérez Ana María, Carrillo-Dávila Irving Alejandro, Rosales-Reynoso Mónica Alejandra, Dávalos-Rodríguez Ingrid Patricia, Delgado-Saucedo Jorge I, López-Monroy Marco Uriel
División de Genética, Centro de Investigación Biomédica de Occidente, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Col. Independencia, Guadalajara 44340, Jalisco, Mexico.
Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Diseases. 2024 Nov 2;12(11):276. doi: 10.3390/diseases12110276.
This study investigated the association between the rs13306703 and rs8192288 variants of the superoxide dismutase 3 () gene and breast cancer (BC) in the Mexican population, conducting both genetic and in silico analyses. 357 healthy women and 386 BC patients were studied using TaqMan assays, qPCR, and RFLP-PCR. The genotype and a recessive pattern of these variants were risk factors for BC ( < 0.05). Specifically, the 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 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 genotype combined with DM was identified as a BC risk factor ( < 0.05). The haplotype was also found to be a risk factor for BC. In silico analysis suggested that these variants might influence regulation by affecting transcription factors and active enhancer sites. The rs13306703 and rs8192288 variants of the gene were associated with an increased risk of BC and may alter regulation through effects on transcription factors, active enhancers, and transcription start sites, with modified motifs in breast epithelium cells.
本研究通过基因分析和计算机模拟分析，调查了墨西哥人群中超氧化物歧化酶3（SOD3）基因的rs13306703和rs8192288变体与乳腺癌（BC）之间的关联。使用TaqMan检测、定量聚合酶链反应（qPCR）和限制性片段长度多态性聚合酶链反应（RFLP-PCR）对357名健康女性和386名BC患者进行了研究。这些变体的特定基因型和隐性模式是BC的危险因素（P<0.05）。具体而言，rs13306703的特定基因型与转移性淋巴结、肿瘤进展（III-IV期）、腔面A型、化疗无反应以及糖尿病（DM）患者中Ki-67≥20%相关。同时，rs8192288的特定基因型与绝经、腔面A型、肿瘤进展（III-IV期）、Ki-67≥20%以及雌激素受体阳性且化疗无反应相关。此外，特定基因型与DM相结合被确定为BC的危险因素（P<0.05）。该单倍型也被发现是BC的危险因素。计算机模拟分析表明，这些变体可能通过影响转录因子和活性增强子位点来影响SOD3的调控。SOD3基因的rs13306703和rs8192288变体与BC风险增加相关，可能通过影响转录因子、活性增强子和转录起始位点来改变SOD3调控，并在乳腺上皮细胞中具有修饰的基序。
