In these paired cell lines with different ZNF423 rs9940645SNP genotypes, we validated the results observed in LCLs and breast cancer cells in that knocking down CALML3 abolished the SNP-dependent gene regulation of ZNF423 and BRCA1 expression in cells treated with E2 ± SERMs (Fig. 3a, b; Additional file 2: Figure S3E, F).The binding of CALML3 and ERα to the genomic region containing the SNP in the presence of E2 ± SERM treatment was also investigated. Here, BRCA1 is linked to breast cancer.