In the field of breast cancer, the clinical value of SMRGs has been verified: for example, aromatase encoded by CYP19A1 is a key rate-limiting enzyme in estrogen synthesis, and its inhibitors have become standard therapeutic agents for ER-positive breast cancer by reducing estrogen production (7); both two-sample Mendelian randomization studies and epidemiological data have shown that elevated levels of total testosterone and bioavailable testosterone increase the risk of ER+ breast cancer, with this association being more pronounced in postmenopausal women (8, 9). The gene discussed is ESR1; the disease is breast carcinoma.