Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2) Polymorphisms in Breast Carcinoma

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).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 decreasesd 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.The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.Breast carcinoma is the most frequent malignancy in women [1] and represents the second leading cause of cancer death among women (15% of cancer deaths) [2]. With 200,000 cases in the U.S.A. (27% of all cancers in women) [3]; 320,000 cases in Europe (31% of all cancers in women) [4] and one million new cases diagnosed worldwide every year, breast carcinoma is still a major health problem in many developed countries. In Tunisia, breast carcinoma accounts for 20–25% of malignant tumors in women with an annual incidence of about 800–1000 cases [5]. The etiology of breast carcinoma is st