Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such asKEAP1(rs1048290) andNRF2(rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions.
乳腺癌仍是女性癌症死亡的首要原因。长期雌激素暴露因其导致半醌类物质生成及解毒功能受损而被视为致癌因素。代谢调节基因多态性，如KEAP1(rs1048290)和NRF2(rs35652124、rs6721961、rs6706649)，对理解个体细胞保护特征具有重要价值。本研究旨在对血液、肿瘤及癌旁组织中的这些多态性进行基因分型，以识别体细胞突变并分析其与预后的相关性。共纳入23名对照者和69名经组织学确诊的乳腺癌患者，对其血液/癌旁/肿瘤组织的DNA进行基因分型，并将分型结果与临床病理资料进行关联分析。研究发现rs35652124在血液/癌旁组织(p=0.023)及肿瘤/癌旁组织(p=0.041)间存在基因型分布差异。除rs35652124外，结合组织学分级分析，其余四个多态性在不同组织中也呈现分布差异。与血液和肿瘤组织相比，癌旁组织存在杂合性缺失趋势，且组织学2级中基因型变异度更高。这些体细胞突变及差异分布模式可能提示存在异质性活跃的微环境，进而影响乳腺癌预后。此外，结合体细胞突变谱及分布特征评估组织学2级的预测价值具有重要临床意义。
肿瘤(癌症)患者之家