Importance of CYP1A1 polymorphism and its transcriptional regulation in ovarian and endometrial cancer

Abstract

Human cytochrome P450 1A 1 is one of the most important enzymes participating in human carcinogenesis because it metabolites several procarcinogens to active carcinogenic metabolites. Additionally enzymes of CYP450 family play an important role in estrogenes catabolization (17-beta-estradiol and estron) to intermediate products (2-, 4-hydroxyestradiol and 2-, 4-hydroxyestrone) including CYP1A1 that catalyses hydroxylation to 2-hydroxyestrogens in the endometrium. Derivates of these compounds (4-hydroxyestrogens) are carcinogenic and could induce DNA damage leading to tumour transformation. The presence of CYP1A1 enzyme in genital tract tissues could induce chemical carcinogenesis initiating cancer development. Recent studies also confirmed the role of CYP1A1 in the development of ovarian and endometrial cancer in humans. The presence of mutated CYP1A1 polymorphic variants influencing the CYP1A 1 activity could be responsible for different interindividual susceptibility to genital cancers in women.