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J Appl Toxicol ; 33(9): 906-14, 2013 Sep.
Article in English | MEDLINE | ID: mdl-22729568

ABSTRACT

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.


Subject(s)
Carcinogens/toxicity , Lung Neoplasms/blood , Occupational Exposure/analysis , Polychlorinated Biphenyls/blood , Adult , Aged , Aged, 80 and over , Body Mass Index , Carcinogens/administration & dosage , Case-Control Studies , Catechol O-Methyltransferase/metabolism , Catechol O-Methyltransferase Inhibitors , Catechols/metabolism , Cell Proliferation/drug effects , Cytochrome P-450 CYP1A1/blood , Cytochrome P-450 CYP1A1/genetics , DNA Damage/drug effects , Female , Genotype , Humans , Life Style , Lung/cytology , Lung/drug effects , Lung/pathology , Lung Neoplasms/chemically induced , Male , Middle Aged , Occupational Exposure/adverse effects , Odds Ratio , Oxidative Stress/drug effects , Polychlorinated Biphenyls/adverse effects , Polymorphism, Genetic , Risk Factors , Socioeconomic Factors , Surveys and Questionnaires , Young Adult
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