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

Abstract

BackgroundXenobiotic 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.MethodsThe 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).ResultsThe 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.ConclusionThe present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.

Low Microsomal Epoxide Hydrolase Expression is Associated with Bladder Carcinogenesis and Recurrence

“…Our results indicate that there was a significantly higher mEH expression in normal epithelium than those in bladder urothelial carcinoma (P<0.05) and there was lower mEH level in more higher histological grade, higher pT stage and more likely to relapse (P<0.05). These data were the same with previous reports about mEH was related with carcinoma (Kang et al, 2004;Nock et al, 2007;Hsu et al, 2008;Khedhaier et al, 2008;Lacko et al, 2009;Erkisi et al, 2010;Ihsan et al, 2010). These findings suggest the important role of mEH in bladder carcinogenesis, cancer development and recurrence, which support the effort to additionally investigate a mEH -based gene therapy.…”

Meta-analysis of microsomal epoxide hydrolase gene polymorphism and the risk of breast carcinoma

“…Five of the 7 studies were conducted in a Caucasian population (de Assis et al, 2002;Sarmanová et al, 2004;Spurdle et al, 2007;Justenhoven et al, 2008;Abbas et al, 2010). The other 2 studies were in African (Khedhaier et al, 2008) and Asian (Sangrajrang et al, 2009) populations. The polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 4 studies (de Assis et al, 2002;Sarmanová et al, 2004;Justenhoven et al, 2008;Khedhaier et al, 2008).…”

“…Although we also searched for relevant genome-wide association studies, we found no studies investigating the association between mEH Tyr113His and His139Arg polymorphisms and risk of breast carcinoma. Only 7 studies (de Assis et al, 2002;Sarmanová et al, 2004;Spurdle et al, 2007;Justenhoven et al, 2008;Khedhaier et al, 2008;Sangrajrang et al, 2009;Abbas et al, 2010), involving 6357 breast carcinoma cases and 8090 healthy controls, were included in this metaanalysis (Tables 1 and 2). All patients in the case group had incident primary breast carcinoma.…”

The EPHX1 rs1051740 Polymorphism Is Associated with Childhood Acute Lymphoblastic Leukemia in a Korean Population

“…However, the many studies that have investigated this have produced inconsistent findings. The Tyr113His polymorphism has been associated with, in most studies, an increased risk for various cancers, such as lung [20] [24] [25], ovarian [26], esophageal [27], breast [28], and bladder [29] cancer and, in a few studies, a decreased risk of childhood ALL [7] and lung cancer [30]. In contrast, the His139Arg polymorphism has no association with many cancers [11] [27] [29] [31].…”