Background: Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor α and estrogen receptor β occur during breast cancer development and both genes polymorphisms have been found to be associated with breast cancer and clinical features of the disease in the western countries. In the current study, we evaluated the hypothesis that certain sequence variants of the ER-α and ER-β genes are associated with an additively increased risk for breast cancer in Iranian women breast cancer patients.

Methods: The genes were scanned in 150 Iranian patients with newly diagnosed invasive breast tumors and in healthy control individuals by PCR single-strand conformation polymorphism (SSCP) method.

Results: Three SNPs rs2077647، rs1801132، rs2228480، in ER-α gene and one SNP rs1256054 in ER-β were revealed have additive effects in developing breast cancer and LN metastases. Also, SNP in codon 392 of estrogen receptor-β gene is more effective (10 folds and three folds) than those SNPs in codons 10, 325, 594 of estrogen receptor-α gene in developing familial breast cancer and LN metastases in breast cancer patients respectively.

Conclusion:  SNPs in estrogen receptor α and β have additive effects in increasing risk for developing familial breast cancer and breast LN metastases among Iranian women breast cancer patients and furthermore SNP in codon 392 of estrogen receptor-β gene is more effective.