RESUMEN
Lung cancer is the most common cancer in the world. The main cause of lung cancer is cigarette smoke; however, other important genetic and environmental risk factors play a significant role in the development of lung cancer. Among these factors, occupational and accidental exposure to polychlorinated biphenyls (PCBs) has been associated with an increased risk in lung cancer, suggesting that PCBs could be potent carcinogens. The aim of the present study was to investigate the association between PCB exposure levels, CYP1A1 polymorphisms and the risk of lung cancer. This study enrolled newly diagnosed lung cancer patients. Environmental and occupational information related to the patients studied was collected. Blood samples were taken for the measurement of serum levels of 20 PCB congeners and for CYP1A1 polymorphism analysis. The serum levels of two PCB congeners with potential estrogenic activity were higher in lung cancer patients. The risk of lung cancer was found to correlate with age, gender, smoking history and with agricultural workers, as well as with congener 18. No differences were found in the frequency of CYP1A1 polymorphisms. Furthermore, we did not find a correlation between CYP1A1 polymorphisms and PCB serum levels. The high levels of PCB with estrogenic activity found in our cases, could promote lung cancer inducing cell proliferation in non-neoplastic and neoplastic lung cells via ERß; inducing the formation of DNA adducts, producing oxidative stress with the subsequent DNA damage and increasing the endogenous catechol levels by catechol-O-methyl transferase (COMT) inhibition.
Asunto(s)
Carcinógenos/toxicidad , Neoplasias Pulmonares/sangre , Exposición Profesional/análisis , Bifenilos Policlorados/sangre , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Carcinógenos/administración & dosificación , Estudios de Casos y Controles , Catecol O-Metiltransferasa/metabolismo , Inhibidores de Catecol O-Metiltransferasa , Catecoles/metabolismo , Proliferación Celular/efectos de los fármacos , Citocromo P-450 CYP1A1/sangre , Citocromo P-450 CYP1A1/genética , Daño del ADN/efectos de los fármacos , Femenino , Genotipo , Humanos , Estilo de Vida , Pulmón/citología , Pulmón/efectos de los fármacos , Pulmón/patología , Neoplasias Pulmonares/inducido químicamente , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Oportunidad Relativa , Estrés Oxidativo/efectos de los fármacos , Bifenilos Policlorados/efectos adversos , Polimorfismo Genético , Factores de Riesgo , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Alteration of multidrug resistance-associated protein-1 (MRP1) expression has been associated with certain lung diseases, and this protein may be pivotal in protecting the lungs against endogenous or exogenous toxic compounds. The aim of this study was to evaluate and compare the expression of MRP1 in bronchoalveolar cells from subjects with and without lung cancer who had been chronically exposed to arsenic through drinking water. MRP1 expression was assessed in bronchoalveolar cells in a total of 102 participants. MRP1 expression was significantly decreased in those with arsenic urinary levels >50 µg/L when compared with the controls. In conclusion, chronic arsenic exposure negatively correlates with the expression of MRP1 in BAL cells in patients with lung cancer.