GENETIC POLYMORPHISMS IN THE ESTROGEN RECEPTOR α GENE CODON 325(CCC-CCG) an‎d RISK OF BREAST CANCER AMONG IRANIAN WOMEN: A CASE CONTROL STUDY

Background: The Iranian breast cancer patients are relatively younger than their Western counterparts. Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor-a (ER-a), occur during breast cancer development in Caucasians. Epidemiologic studies have revealed that age-incidence patterns of breast cancer in Asians differ from those in Caucasians. Genomic data for ER-a in either population is therefore of value in the clinical setting for the Iranian breast cancer. Methods: A case-control study was conducted to establish a database of ERpolymorphisms in Iranian women population in order to compare Western and Asian with Iranian (Asian-Caucasians) distributions and to evaluate ER- polymorphism as an indicator of clinical outcome. DNA samples were prepared from Iranian women with breast cancer referred to Imam Khomeini Hospital Complex clinical breast cancer group (150 patients) and in healthy individuals (147 healthy control individuals). PCR single-strand conformation polymorphism technology was performed. Results: Asite of silent single nucleotide polymorphism (SNP) was found, as reported previously in Western and Eastern studies, but at significantly different frequencies. The frequency of allele 1 in codon 325 (CCC®CCG) was significantly higher in the breast cancer patients (39.6%) than control individuals (28.9%; P= 0.007). The allele 1 had also significant association with the occurrence of lymph node metastasis. Conclusion: Data suggested that ER-a polymorphisms in exon 4 codon 325 was correlated with various aspects of breast cancer in Iran. ER-a genotype, as determined during presurgical evaluation, might represent a surrogate marker for predicting the breast cancer lymph node metastasis.