Xenobiotic metabolizing enzyme polymorphisms and survival in lung cancer patients

Abstract

Event Abstract Back to Event Xenobiotic metabolizing enzyme polymorphisms and survival in lung cancer patients Mumtaz Iscan1* 1 Ankara University, Department of Toxicology, Türkiye Lung cancer is an increasing worldwide public health problem particularly in men and has two histological types, namely small cell lung carcinoma (SCLC) and non small cell lung carcinoma (NSCLC). Approximately 80 % of lung carcinomas have NSCLC histology. In the patients with NSCLC platinum based chemotherapy and chemoradiotherapy are standard treatment strategies. The response to chemotherapy particularly for patients with NSCLC has been reported to be rather poor. Thus, the investigation of the reasons behind this failure of chemotherapy, and thus possibly poorer survival in these patients is very important. It is well known that most of the lung cancer patients are cigarette smokers. Cigarette smoke has been reported to cause elevated levels of carcinogen DNA-adducts which in turn form aggressive tumors by mutating and thus inactivating tumor suppressor genes (such as p53) and thereby decrease the survival rates of patients with NSCLC . Metabolic activation of polycyclic aromatic hydrocarbons (PAHs) and nitrosamines in cigarette smoke to mutagenic and carcinogenic metabolites are mediated by CYPs namely CYP1A1, CYP1B1 and CYP2E1. In addition, these CYPs play a role in the metabolism of a number of drugs including chemotherapeutic agents and thus involve in drug resistance. These CYP genes have been found to be polymorphic and the most common alleles and polymorphisms of these CYPs have altered enzyme activities. Glutathione S-transferases (GST)s are involved in the inactivation of various carcinogenic compounds found in cigarette smoke that are activated by CYPs but on the other hand also play an important role in the resistance of lung cancer therapy especially to platinum compounds. GSTs decrease the cytotoxic impact of these chemotherapeutic drugs. However, certain polymorphisms in GSTs are associated with changes or loss in enzyme activity. Since CYPs and GSTs catalyze several chemotherapeutic agents and reactive metabolites including by-products of reactive oxygen species which damage the DNA, lung cancer patients may differ in response to therapy, depending on CYP and GST activity. Thus, CYP and GST genotypes may have influence on the response to therapy and survival of the lung cancer patients. Herein, recent findings with respect to the role of CYP and GST gene polymorphisms in response to therapy and survival in lung cancer patients will be evaluated (Supported by the Research Fund of Ankara University grants; 20060803002HPD, 20070803005 HPD, 20080803006HPD, 10A3336002). Keywords: cytochrome P450, Glutathione S-transferase, polymorphism, lung cancer, Survival, chemotherapy, cigarette smoke Conference: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010. Presentation Type: Invited speaker Topic: Genomics - Proteomics - Metabolomics Citation: Iscan M (2010). Xenobiotic metabolizing enzyme polymorphisms and survival in lung cancer patients. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010. doi: 10.3389/conf.fphar.2010.60.00131 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Mar 2011; Published Online: 04 Nov 2010. * Correspondence: Dr. Mumtaz Iscan, Ankara University, Department of Toxicology, Ankara, Türkiye, Mumtaz.Iscan@pharmacy.ankara.edu.tr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mumtaz Iscan Google Mumtaz Iscan Google Scholar Mumtaz Iscan PubMed Mumtaz Iscan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.