Faculty of Sciences, El-Manar University, Tunis, Tunisia.
Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
Gene. 2023 Jan 30;851:146969. doi: 10.1016/j.gene.2022.146969. Epub 2022 Oct 17.
We previously reported on the association between ESR1 and ESR2 gene variants and heightened risk of breast cancer (BC). Here we investigated the association of common ESR1 and ESR2 gene variants with triple negative BC (TNBC).
This retrospective case-control study involved 488 BC patients (130 TNBC, 358 non-TNBC patients). ESR1 (rs2234693, rs9340799, rs3020314, rs3798577) and ESR2 (rs928554, rs944459, rs4986938, rs1256049, rs1256030, rs1271572) genotyping was done by real-time PCR.
While minor allele frequencies (MAF) of ESR1 variants were comparable between TNBC and non-TNBC subjects, significantly higher ESR2 rs1256049 MAF was seen in TNBC patients. Significantly higher frequency of ESR1 rs3798577 T/C and C/C genotypes were noted in TNBC cases, and significant differences were seen in ESR2 rs928554, rs1256049, and rs1271572 genotype distribution. Increased TNBC risk was associated with ESR1 rs3798577 T/C and C/C genotypes according to codominant and dominant models, while positive association of ESR2 rs928554 with TNBC was seen according to codominant and recessive models, and positive association of ESR2 rs1256049 with TNBC was seen according to codominant and dominant models. Positive interactions were noted between ESR2 rs1271572-ESR1 rs3020314, ESR2 rs1271572-ESR1 rs9340799, and ESR2 rs1271572-ESR1 rs2234693, ESR2 rs4986938-ESR1 rs2234693, and ESR2 rs928554-ESR1 rs9340799. Haplotype analysis confirmed the positive association of ESR1 CATT with TNBC, while ACGGCTC and ACGGTT ESR2 haplotypes were positively associated with TNBC.
Results of this study confirmed the association of unique ESR1 and ESR2 genetic variants with altered risk of TNBC. This suggests possible diagnostic and prognostic role of these variants with TNBC independent of their association with BC.
我们之前报道了 ESR1 和 ESR2 基因变异与乳腺癌（BC）风险增加之间的关联。在这里，我们研究了常见的 ESR1 和 ESR2 基因变异与三阴性乳腺癌（TNBC）的关系。
本回顾性病例对照研究纳入了 488 例 BC 患者（130 例 TNBC，358 例非 TNBC 患者）。通过实时 PCR 对 ESR1（rs2234693、rs9340799、rs3020314、rs3798577）和 ESR2（rs928554、rs944459、rs4986938、rs1256049、rs1256030、rs1271572）基因进行了分型。
虽然 TNBC 和非 TNBC 患者的 ESR1 变体的次要等位基因频率（MAF）相似，但在 TNBC 患者中观察到 ESR2 rs1256049 MAF 显著升高。在 TNBC 病例中，ESR1 rs3798577 T/C 和 C/C 基因型的频率明显更高，ESR2 rs928554、rs1256049 和 rs1271572 基因型分布也存在显著差异。根据共显性和显性模型，ESR1 rs3798577 T/C 和 C/C 基因型与 TNBC 风险增加相关，而 ESR2 rs928554 与 TNBC 呈共显性和隐性相关，ESR2 rs1256049 与 TNBC 呈共显性和显性相关。ESR2 rs1271572-ESR1 rs3020314、ESR2 rs1271572-ESR1 rs9340799 和 ESR2 rs1271572-ESR1 rs2234693 之间存在阳性相互作用，ESR2 rs4986938-ESR1 rs2234693 和 ESR2 rs928554-ESR1 rs9340799 之间也存在阳性相互作用。单体型分析证实了 ESR1 CATT 与 TNBC 的正相关，而 ACGGCTC 和 ACGGTT ESR2 单体型与 TNBC 呈正相关。
本研究结果证实了独特的 ESR1 和 ESR2 遗传变异与 TNBC 风险改变之间的关联。这表明这些变异与 TNBC 的可能具有诊断和预后作用，而与它们与 BC 的关联无关。
