Association of estrogen receptor 1 (ESR1) gene (rs2234693) polymorphism, ESR1 promoter methylation status, and serum heavy metals concentration, with breast cancer: A study on Iranian women population

Background: genetic and epigenetic alteration of estrogen receptor genes could be associated with the devel-opment of breast cancer. In addition, demographic and environmental factors may play a role in this issue. This work was performed to investigate the effect of Estrogen Receptor 1 (ESR1) puv II (rs2234693 T > C) polymorphism, the methylation status of ESR1 promoter as well as the serum level of different heavy metals, including lead, cadmium, zinc, copper, and chromium on susceptibility to breast cancer. Material and methods: 60 breast cancer patients and 60 healthy controls from the province of Mazandaran, Iran, participated in this case-control study. Restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and Quantitative methylation-specific PCR were conducted to determine ESR1 PvuII (rs2234693 T > C) polymorphism and methylation status of ESR1 promoter, respectively. Also, flame atomic absorption was used to determine the serum level of heavy metals. Result: The association of TC and CC + TC genotypes with a higher risk of breast cancer was found. In addition, no difference for the methylation status of ESR1 promoter among case and control individuals was observed. In addition, there was an association between serum level of chromium with breast cancer, while the serum level of other heavy metals was not significantly different between the two groups. Conclusion: our study suggests ESR1 polymorphism and environmental pollutants as two main contributing factors in breast cancer susceptibility in Iranian women. However, further investigations are needed on this issue.