title: Variability in estrogen-metabolizing genes and their association with genomic instability in untreated breast cancer patients and healthy women.
abstract: In the present study, we investigated the relationship between polymorphisms in the estrogen-metabolizing genes CYP17, CYP1B1, CYP1A1, and COMT and genomic instability in the peripheral blood lymphocytes of 62 BC patients and 62 controls considering that increased or prolonged exposure to estrogen can damage the DNA molecule and increase the genomic instability process in breast tissue. Our data demonstrated increased genomic instability in BC patients and that individuals with higher frequencies of MN exhibited higher risk to BC when belonging Val/Met genotype of the COMT gene. We also observed that CYP17 and CYP1A1 polymorphisms can modify the risk to BC depending on the menopause status. We can conclude that the genetic background in estrogen metabolism pathway can modulate chromosome damage in healthy controls and patients and thereby influence the risk to BC. These findings suggest the importance to ally biomarkers of susceptibility and effects to estimate risk groups.
authors.affiliation: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Bloco G., Avenue Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil. rasantos@rge.fmrp.usp.br
authors.forename: Raquel Alves
authors.initials: RA
authors.lastname: dos Santos
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Teixeira
authors.forename: Mônica Beatriz
authors.initials: MB
authors.lastname: Mayorano
authors.forename: Hélio Humberto Angotti
authors.initials: HH
authors.lastname: Carrara
authors.forename: Jurandyr
authors.initials: J
authors.lastname: de Andrade
authors.forename: Catarina Satie
authors.initials: CS
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D004967:Estrogens; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D013254:Steroid 17-alpha-Hydroxylase; D002394:Catechol O-Methyltransferase