Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2) polymorphisms in breast carcinoma.
BMC Cancer
; 8: 109, 2008 Apr 18.
Article
em En
| MEDLINE
| ID: mdl-18423013
ABSTRACT
BACKGROUND:
Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients.METHODS:
The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients).RESULTS:
The mEH (C/C) mutant and the NAT2 slow acetylator genotypes were significantly associated with breast carcinoma risk (p = 0.02; p = 0.01, respectively). For NAT2 the association was more pronounced among postmenopausal patients (p = 0.006). A significant association was found between CYP2D6 (G/G) wild type and breast carcinoma risk only in postmenopausal patients (p = 0.04). Association studies of genetic markers with the rates of breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) revealed among all breast carcinoma patients no association to DFS but significant differences in OVS only with the mEH gene polymorphisms (p = 0.02). In addition, the mEH wild genotype showed a significant association with decreased OVS in patients with axillary lymph node-negative patients (p = 0.03) and with decreased DFS in patients with axillary lymph node-positive patients (p = 0.001). However, the NAT2 intermediate acetylator genotype was associated with decreased DFS in axillary lymph node-negative patients.CONCLUSION:
The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Arilamina N-Acetiltransferase
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Neoplasias da Mama
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Xenobióticos
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Citocromo P-450 CYP2D6
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Epóxido Hidrolases
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article