Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer

Abstract EN

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.