However, compounds that engage either nuclear ER (ERα and ERβ) can also increase the risk of a variety of cancers (Coman et al., 2017; Liu et al., 2018; Tao et al., 2018) as well as other deleterious cellular responses, including mitochondrial dysfunction (Burstein et al., 2018; Colon-Caraballo, 2019). This evidence concerns the gene ESR2 and cancer.