AOS19 Oestrogen receptor-[formula omitted] gene polymorphism (T392C) in Iranian women with breast cancer

Abstract

Background Receptor-mediated oestrogen activation plays a part in the development and progression of breast cancer. Evidence suggests that alterations in oestrogen signalling pathways, including oestrogen receptor- α (ESR1- α ) occur during breast cancer development. ESR1- α gene polymorphism is known to be associated with breast cancer and clinical features of the disease in Caucasians. Results of epidemiological studies have shown that age-incidence patterns of breast cancer in women from the Middle East differ from those in Caucasians. Genomic data for ESR1- α in either population are therefore important in the clinical setting for each ethnic group and we have investigated whether polymorphisms in the ESR1- α are associated with risk of breast cancer. Methods A case–control study was done to establish a database of ESR1 polymorphisms in the Iranian population for comparison of western and Iranian (Middle East) distributions and to assess ESR1 polymorphism as an indicator of clinical outcome. The ESR1 gene was scanned in 150 Iranian patients who were newly diagnosed with invasive breast tumours and in 147 healthy individuals. Single-strand conformation polymorphism polymerase chain reaction (PCR) and direct sequencing were done. Findings Silent single nucleotide polymorphisms (SNPs), as reported in previous studies, were found but at significantly different frequencies. The frequency of allele 1 in codon 10 (TCT → TCC) (T/C, S392S) of exon 1 was significantly higher in patients with breast cancer (45.7%) than in the controls (39.8%; p = 0.148). We found that allele 1 (TCT → TCC) in codon 10 was significantly more common in patients with breast cancer who had 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 showed an association with the occurrence of lymph node metastasis (58.7% and 43.3% with and without lymph node metastases, respectively). Therefore, this SNP marker further increased predictive accuracy in the Iranian population. Interpretation Our data suggest that ESR1 polymorphisms correlated with various aspects of breast cancer in Iranian women, as determined during pre-surgical assessment, might represent a surrogate marker for predicting breast cancer. The authors declared no conflicts of interest.