In addition to the use of breast cancer or BRCA1/2 mutation status as the primary variable, Crooke et al. developed a model for looking at the kinetic effect of genetic variants of the enzymes CYP1A1, CYP1B1, and COMT as well as phenotype factors on the production of the main carcinogenic estrogen metabolite 4-hydroxyestradiol (4-OHE(2)), expressed as an AUC metric (4-OHE(2)-AUC) [62]. The gene discussed is BRCA1; the disease is breast cancer.