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Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 2769804, 7 pages
http://dx.doi.org/10.1155/2016/2769804
Research Article

Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer

1Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
2Instituto de Investigação Científica Bento da Rocha Cabral, 1250-047 Lisbon, Portugal
3Dermatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1250-047 Lisbon, Portugal
4Clinical and Translational Oncology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1250-047 Lisbon, Portugal
5Molecular Oncology Group, Portuguese Institute of Oncology Porto Centre, 4200-072 Porto, Portugal

Received 24 May 2015; Revised 30 September 2015; Accepted 1 October 2015

Academic Editor: Valentina Pallottini

Copyright © 2016 Andreia Matos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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, ). The allele C of CYP1A1 was a risk for c-cancer (OR = 2.29, ). Women with COMT LL genotype had a higher risk of developing c-cancer (OR = 4.83, ). For the interaction of the CYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07, ) and TT&HL genotypes had a protection effect (OR = 0.24, ). The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c-cancer ( and , 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.