Almeida Micaela, Ferreira Catarina L, Tomé Rosa Maria, Fonseca-Moutinho José, Polónia António, Ramalhinho Ana Cristina, Breitenfeld Luiza
Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal.
Clinical Academic Centre of Beiras (CACB), Edifício UBImedical, Estrada Municipal 506, 6200 Covilhã, Portugal.
Cancers (Basel). 2024 Jun 29;16(13):2411. doi: 10.3390/cancers16132411.
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 as (rs1048290) and (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 (-value = 0.023) and tumour/surrounding tissues (-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.
乳腺癌仍然是女性癌症死亡的主要原因。长期雌激素暴露由于半醌的产生和解毒功能受损而被认为具有致癌性。代谢调节因子多态性，如（rs1048290）以及（rs35652124、rs6721961、rs6706649），对于了解个体细胞保护情况可能具有重要价值。因此，我们旨在对血液、肿瘤及周围组织中的这些多态性进行基因分型，以识别体细胞突变并将其与预后相关联。总共招募了23名对照者和69名经组织学确诊的乳腺癌女性，并对血液/周围组织/肿瘤组织的DNA进行基因分型。对基因分型和临床病理数据进行了相关性分析。我们证实，rs35652124在血液/周围组织（P值 = 0.023）和肿瘤/周围组织（P值 = 0.041）之间呈现出不同的基因型分布。除rs35652124外，考虑到组织学分级，其他四个多态性在不同组织间具有不同的分布。与血液和肿瘤组织相比，周围组织存在杂合性缺失的趋势，且在组织学2级中基因型变异性更高。这些体细胞突变和不同的分布模式可能表明存在异质性且活跃的微环境，影响乳腺癌的预后。此外，考虑体细胞突变谱和分布来评估组织学2级的预测价值将是有意义的。
