CYP3A53 genotypes and advanced non-small cell lung cancer development

• Published in: Journal of clinical oncology Vol. 25; no. 18_suppl; p. 21030
• Main Authors: Nogal, A., Coelho, A., Araújo, A., Azevedo, I., Faria, A., Soares, M., Catarino, R., Medeiros, R.
• Format: Journal Article
• Language: English
• Published: 20-06-2007
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2007.25.18_suppl.21030

Abstract only 21030 Background: Lung cancer is the most common cancer in Europe (381.500 new cases in 2004) and the third in the U.S.A (172.570 new cases in 2005). Smoking is one of the major causes of lung cancer: there are many procarcinogens present in tobacco smoke that, when activated, contribute to the development of this disease. The CYP3A subfamily represents a group of enzymes responsible for the metabolism of many currently used drugs, exogenous carcinogens and endogenous molecules such as steroids. Two of the major enzymes in this family, CYP3A4 and CYP3A5, activate polycyclic aromatic hydrocarbons such as benzo[a]pyrene and other procarcinogens present in tobacco smoke. Functional polymorphisms, such as CYP3A5*3 (associated with the lack of the CYP3A5 protein), could alter individual susceptibility to lung cancer. The aim of our study was to evaluate the influence of this polymorphism in the development of lung cancer. Methods: DNA samples were extracted from peripheral blood cells of 203 patients with non small cell lung cancer, including 42 non- smokers and 156 smokers or former smokers (no data available for the other 5 patients) and 162 blood donors. The CYP3A5*3 polymorphism was analysed through PCR-RFLP (SspI). Analysis of data was performed using the computer software SPSS for windows. The odds ratio (OR) and its 95% confidence interval (CI) were calculated as a measure of the association between CYP3A5*3 genotypes and NSCLC progression. Results: We found significant statistical differences between the control group and the patients with advanced stages (III and IV) of epidermoid and undifferentiated NSCLC (p=0.04; OR = 0.48; 95% CI = 0.232–0.977). Conclusions: Individual differences in the metabolism of carcinogens may influence the susceptibility to cancer development and behaviour. Our preliminary results suggest that the carriers CYP3A5*3 polymorphism are at lower risk of developing advanced lung cancer. This is probably due to a decreased activation of procarcinogens present in tobacco smoke in result of the lack of CYP3A5 caused by the CYP3A5*3 polymorphism. This is consistent with the hypothesis of a cumulative effect of carcinogens on the aggressive behaviour of the disease. No significant financial relationships to disclose.