title: Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer.
abstract: 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.
authors.affiliation: Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; Instituto de Investigação Científica Bento da Rocha Cabral, 1250-047 Lisbon, Portugal.
authors.forename: Andreia
authors.identifier: 0000-0003-1551-9465
authors.initials: A
authors.lastname: Matos
authors.affiliation: Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; Dermatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1250-047 Lisbon, Portugal.
authors.forename: Cindy
authors.initials: C
authors.lastname: Castelão
authors.affiliation: Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; Instituto de Investigação Científica Bento da Rocha Cabral, 1250-047 Lisbon, Portugal.
authors.forename: Alda
authors.initials: A
authors.lastname: Pereira da Silva
authors.affiliation: Clinical and Translational Oncology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1250-047 Lisbon, Portugal.
authors.forename: Irina
authors.initials: I
authors.lastname: Alho
authors.affiliation: Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; Instituto de Investigação Científica Bento da Rocha Cabral, 1250-047 Lisbon, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bicho
authors.affiliation: Molecular Oncology Group, Portuguese Institute of Oncology Porto Centre, 4200-072 Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.affiliation: Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; Dermatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1250-047 Lisbon, Portugal.
authors.forename: Maria Clara
authors.initials: MC
authors.lastname: Bicho
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004843:Epistasis, Genetic; D004958:Estradiol / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics*; D055815:Young Adult
chemical_list: D004958:Estradiol; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase