Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2) polymorphisms in breast carcinoma.
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.


CONCLUSIONS
The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.
Khedhaier
Achraf
A
Laboratoire d'Immuno-Oncologie Moleculaire, Faculté de Médecine de Monastir, Tunisia. a_khedhaier@yahoo.fr
Hassen
Elham
E
Bouaouina
Noureddine
N
Gabbouj
Sallouha
S
Ahmed
Slim Ben
SB
Chouchane
Lotfi
L
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D018572:Disease-Free Survival; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015262:Xenobiotics / Q000493:pharmacokinetics*
D015262:Xenobiotics; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D004851:Epoxide Hydrolases