rs2077647 polymorphism in ESR1 gene on breast cancer risk

Introduction: Receptor-mediated estrogen activation participates in the development and progression of breast cancer. Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor-α (ESR1) occur during breast cancer development. Estrogen receptor-α gene (ESR1) polymorphism has been found to be associated with breast cancer and clinical features of the disease inCaucasians. Epidemiologic studies have revealed that age–incidence patterns of breast cancer in MiddleEast differ from those in Caucasians. Genomic data for ESR1 in either population is therefore of value in the clinical setting for that ethnic group and we have investigated whether polymorphisms in the ESR1 are associated with breast cancer risk. Methods: A case-control study was conducted to establish a database of ESR1 polymorphisms in Iranian population in order to compare Western and Iranian (Middle East) distributions and to evaluate ESR1 polymorphism as an indicator of clinical outcome. The ESR1 gene was scanned in Iranian patients newly diagnosed invasive breast tumors,(150 patients) and in healthy individuals (147 healthy control individuals). PCR single-strand conformation polymorphism technology and direct sequencing was performed. Results: The silent single nucleotide polymorphism (SNPs) was found, as reported previously in other studies, but at significantly different frequencies. The frequency of allele1 in, codon 10 (TCT → TCC) (T/C, S392S), exon1 was significantly higher in breast cancer patients (45.7%) than in control individuals (39.8%; P= 0.148). We found that allele 1 (TCT→ TCC) in codon10 was significantly more common in breast cancer patients with a family history of breast cancer (78.9%) than in those without such a history (40.8%; P = 0.001). The allele 1 in codon 10 exhibited an association with the occurrence of lymph node metastasis (58.7% and 43.3% with and without LN metastases, respectively). Therefore, this SNP marker further increased predictive accuracy in Iranian population.Conclusions: Our data suggest that ESR1polymorphisms are correlated with various aspects of breast cancer in Iranian ESR1genotype, as determined during pre-surgical evaluation, might represent a surrogate marker for predicting breast cancer

کلیدواژه ها:

breast cancer ، estrogen receptor-α ، polymorphism