Lipworth et al. [20] posited several mechanisms for a pregnancy estrogen effect on breast cancer risk including down-regulation of estrogen receptor expression in breast tissue throughout life, possibly epigenetically mediated, increased mammary cell differentiation (lessening susceptibility to carcinogenesis) from higher levels of pregnancy estrogens interacting with other mammotrophic hormones, and differences in estrogen bioavailability. The gene discussed is ESR1; the disease is breast cancer.