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.
Highlights
Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products
XMEs gene polymorphisms and susceptibility to breast carcinoma The number of polymorphism-genotyped individuals was dependent upon DNA availability
There were no significant differences between patients and controls in the genotype frequencies for CYP2C19, CYP2E1 and CYP2D6 genes (Table 4)
Summary
Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. The etiology of breast carcinoma is still poorly understood in spite of known breast carcinoma risk factors such as age, reproductive events (menarche, menopause, pregnancy, breastfeeding), exogenous hormones (hormone replacement therapy and oral contraceptives), lifestyle and environment risk factors (pollution, alcohol, diet, obesity), ionizing radiation, chemo preventive agents, as well as genetic factors (highand low penetrance breast cancer susceptibility genes) [6]. Mutations in highly penetrant genes such as BRCA1 or BRCA2 confer a relatively high risk for developing breast carcinoma, though this risk accounts only for about 5 to 10% of all breast carcinoma cases [7]. It is suggested that the effect of low penetrance cancer susceptibility genes modulated by environmental exposure and lifestyle factors are likely to account for most of sporadic breast carcinoma cases [8]. The proportion of breast carcinoma attributable to such genetic traits, in combination with environmental exposure, is likely to be much higher than the hereditary proportion and accounts for 90 to 95% of all breast carcinoma cases [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
