Madeira Klesia Pirola, Daltoé Renata Dalmaschio, Sirtoli Gabriela Modenesi, Carvalho Alex Assis, Rangel Leticia Batista Azevedo, Silva Ian Victor
Biotechnology Program/RENORBIO, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil.
Mol Biol Rep. 2014 Aug;41(8):5459-66. doi: 10.1007/s11033-014-3419-8. Epub 2014 Jun 14.
There are several risk factors related to Breast Cancer (BC) risks and response to chemotherapy with SERMs. Recently some single nucleotide polymorphisms (SNPs) on ESR1 gene have been associated to this disease. However, data are still inconclusive. The present study aimed to investigate the association of SNPs c454-397T>C (also called PvuII) and c454-351A>G (so called XbaI) to incidence of sporadic BC; ERα expression in BC; tamoxifen hormonetherapy (HT-TMX) responsiveness. To do so, a cohort of BC patients was analyzed through retrospective data collection, immunohistochemistry to ERα protein, and genotyping for PvuII and XbaI SNPs by PCR-RFLP, confirmed by sequencing. Significant difference in PvuII alleles frequencies were found BC patients when compared to control samples. Patients with P allele have a 5.14-fold increased BC risk. We found higher P and X alleles frequencies in ERα positive BC and the pp and xx genotypes were observed exclusively in patients with HT-TMX-responsive BC. Taken together, data indicates that P allele as a novel sporadic BC biomarker whereas p and x alleles enhanced chemotherapy responsiveness.
有几个与乳腺癌（BC）风险以及对选择性雌激素受体调节剂（SERM）化疗反应相关的风险因素。最近，雌激素受体1（ESR1）基因上的一些单核苷酸多态性（SNP）与这种疾病有关。然而，数据仍然没有定论。本研究旨在调查SNP c454 - 397T>C（也称为PvuII）和c454 - 351A>G（称为XbaI）与散发性BC发病率、BC中雌激素受体α（ERα）表达以及他莫昔芬激素治疗（HT - TMX）反应性之间的关联。为此，通过回顾性数据收集、对ERα蛋白进行免疫组织化学检测以及通过聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）对PvuII和XbaI SNPs进行基因分型，并通过测序进行确认，对一组BC患者进行了分析。与对照样本相比，在BC患者中发现PvuII等位基因频率存在显著差异。携带P等位基因的患者患BC的风险增加5.14倍。我们发现在ERα阳性的BC中P和X等位基因频率更高，并且仅在HT - TMX反应性BC患者中观察到pp和xx基因型。综上所述，数据表明P等位基因是一种新的散发性BC生物标志物，而p和x等位基因增强了化疗反应性。
