ESR1 gene variants, haplotypes and diplotypes may influence the risk of breast cancer and mammographic density.

Breast cancer as the most common cancer worldwide is influenced by genetic and physiological factors. Based on some evidence indicating the role of estrogen receptor 1 gene (ESR1) in breast cancer development, in this study, the association of three common variations in ESR1 gene with breast cancer and density in an Iranian population was evaluated. In a case-control study, 400 blood samples were collected for DNA extraction and genotyping. Breast density was assessed using mammography. ESR1 rs6915267 (G/A), rs2077647 (C/T) and rs1801132 (C/G) were genotyped using ARMS-PCR method. PHASE program was used to estimate the haplotypes frequencies. Our data analysis showed rs6915267 GA genotype in the heterozygous (GA) as well as co-dominant models was associated with lower mammographic density. None of the three variations were associated with the breast cancer risk. Haplotype analysis indicated G-T-C haplotype of rs6915267, rs2077647 and rs1801132 [OR = 0.54, 95% CI (0.31-0.92), p = 0.025] and G-T/G-T diplotype of rs6915267-rs2077647 [OR = 0.38, 95% CI (0.17-0.86), p = 0.019] were associated with a decreased risk of breast cancer. ESR1 may affect density of the breast and its haplotypes may modulate breast cancer risk.