Format

Send to

Choose Destination
Oxid Med Cell Longev. 2016;2016:2769804. doi: 10.1155/2016/2769804. Epub 2015 Dec 21.

Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer.

Author information

1
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.
2
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.
3
Clinical and Translational Oncology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1250-047 Lisbon, Portugal.
4
Molecular Oncology Group, Portuguese Institute of Oncology Porto Centre, 4200-072 Porto, Portugal.

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.

PMID:
26798414
PMCID:
PMC4698955
DOI:
10.1155/2016/2769804
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Hindawi Publishing Corporation Icon for PubMed Central
Loading ...
Support Center