ESR1 and Familial prostate cancer: Aside from apoptosis-related genes, COMT can play a protective role by affecting other pathway genes such as ER-α, p21cip1, p27kip1, NF-κB (P65) and CYP19A1 in prostate cancer [37], cause a reduction in p-AKT, mutant p53, and cyclin D1 but an increase in p-GSK3-b, PTEN and E-cadherin in pancreatic cancer cells [36], and cause inhibition of p-AKT but increased PTEN, p53, p27, and E-Cadherin in colorectal cancer cells [38].