López-Cortés Andrés, Cabrera-Andrade Alejandro, Oña-Cisneros Fabián, Echeverría Carolina, Rosales Felipe, Ortiz Malena, Tejera Eduardo, Paz-Y-Miño César
Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Avenue Mariscal Sucre, 170129, Quito, Ecuador.
Departamento de Patología, Hospital Oncológico Solon Espinosa Ayala, Avenue Eloy Alfaro, 170138, Quito, Ecuador.
Pathol Oncol Res. 2018 Jul;24(3):457-465. doi: 10.1007/s12253-017-0267-6. Epub 2017 Jun 24.
Breast cancer (BC) is the leading cause of cancer related death among women in 2014. The AURKA gene that encodes the protein called Aurora kinase A plays an important role in the progression of the cell cycle, by controlling and promoting the entry into the phase of mitosis. The single nucleotide polymorphism AURKA T91A (rs2273535) (Phe21Ile) has been identified as functional alternator of this kinase, the Ile allele is associated with the occurrence of chromosome segregation errors and tumor progression. Therefore, it is essential to know how BC risk is associated with histopathological characteristics, immunohistochemical characteristics, and genotype polymorphism in a high altitude Ecuadorian mestizo population. In this retrospective case-control study 200 individuals were analyzed. DNA was extracted from 100 healthy and 100 affected women. Genotypes were determined by genomic sequencing. We found significant association between the AURKA T91A (rs2273535) (Phe21Ile) genotype and an increased risk of BC development: Phe/Ile (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.4-4.9; P = 0.004), Ile/Ile (OR = 3.8; 95% CI = 1.6-9.0; P = 0.002), and Phe/Ile + Ile/Ile (OR = 2.9; 95% CI = 1.6-5.2; P = 0.001). Additionally, the rs2273535 variant was associated with the tumor grade SBR III (OR = 9.6; 95% CI = 1.0-91.9; P = 0.048) and the Ki-67 ≥ 20 (OR = 16.5; 95% CI = 2.7-101.3; P = 0.002). In brief, this study provides the first evidence where the Ile allele of the AURKA gene could act as potentially predictive biomarker of BC in the high altitude Ecuadorian mestizo population that lives at 2800 m above sea level (masl).
乳腺癌（BC）是2014年女性癌症相关死亡的主要原因。编码名为极光激酶A的蛋白质的AURKA基因，通过控制和促进进入有丝分裂期，在细胞周期进程中发挥重要作用。单核苷酸多态性AURKA T91A（rs2273535）（Phe21Ile）已被确定为该激酶的功能性交替物，Ile等位基因与染色体分离错误的发生和肿瘤进展相关。因此，了解在厄瓜多尔高海拔梅斯蒂索人群中，BC风险如何与组织病理学特征、免疫组织化学特征和基因型多态性相关至关重要。在这项回顾性病例对照研究中，分析了200名个体。从100名健康女性和100名患病女性中提取DNA。通过基因组测序确定基因型。我们发现AURKA T91A（rs2273535）（Phe21Ile）基因型与BC发生风险增加之间存在显著关联：Phe/Ile（优势比[OR]=2.6；95%置信区间[CI]=1.4 - 4.9；P = 0.004），Ile/Ile（OR = 3.8；95% CI = 1.6 - 9.0；P = 0.002），以及Phe/Ile + Ile/Ile（OR = 2.9；95% CI = 1.6 - 5.2；P = 0.001）。此外，rs2273535变异与肿瘤分级SBR III（OR = 9.6；95% CI = 1.0 - 91.9；P = 0.048）和Ki - 67≥20（OR = 16.5；95% CI = 2.7 - 101.3；P = 0.002）相关。简而言之，本研究提供了首个证据，表明在海拔2800米（masl）的厄瓜多尔高海拔梅斯蒂索人群中，AURKA基因的Ile等位基因可能作为BC的潜在预测生物标志物。
