There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association of CYP1A1 M1 ( rs4646903 ) and COMT ( rs4680 ) polymorphisms in 130 cervical cancer cases (c-cancer) and 179 controls. The CYP1A1 TT genotype was associated with a lower risk for c-cancer (OR = 0.39, p=0.002 ). The allele C of CYP1A1 was a risk for c-cancer (OR = 2.29, p=0.002 ). Women with COMT LL genotype had a higher risk of developing c-cancer (OR = 4.83, p<0.001 ). For the interaction of the CYP1A1 & COMT , we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07, p=0.006 ) and TT&HL genotypes had a protection effect (OR = 0.24, p<0.001 ). The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c-cancer ( p<0.001 and p=0.037 , resp.). C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms of CYP1A1 and COMT , separately. CYP1A1 and COMT work in a metabolic sequence and their interaction could lead to an alternative pathway of estrogen metabolism with production of 16-OH-estrone that is more proliferative.
Matos, A., Castelão, C., Pereira Da Silva, A., Alho, I., Bicho, M., Medeiros, R., & Clara Bicho, M. (2016). Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer. Oxidative Medicine and Cellular Longevity, 2016. https://doi.org/10.1155/2016/2769804