To further determine whether the differential regulation of gene expression in the presence of E2 ± SERMs was due entirely to the SNP effect rather than the heterogeneity of the cancer cells, the ZR75-1 cell line, an ERα + breast cancer cell line that naturally contains the ZNF423 variant SNP genotype, was CRISPR engineered to form the WT sequence. Here, ESR1 is linked to breast cancer.