Role of Detoxifing Enzyme Nicotinamide Adenine Dinucleotide (Phosphate) H: Quinone Oxidoreductase-1 C609t Gene Polymorphism in Bronchogenic Carcinoma
Lung cancer is currently one of the most common cancers and a major cause of cancer-related death in the world. Eighty-five percent of lung cancers are non-small cell lung cancers (NSCLCs), and 15% are small cell lung cancers (SCLCs). The most important risk factor for lung cancer is tobacco smoking. Polycyclic aromatic hydrocarbons (PAHs) are abundant in tobacco smoke and constitute a major etiological factor in lung cancer. NAD (P) H: quinone oxidore – ductase (NQO1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinoid compounds into less toxic hydroquinones. A single base substitution (C→T) polym – orphism at 609 in the NQO1 gene reduces quinone redu – ctase activity. Published data on the association between NQO1609 C˃T polymorphism and lung cancer risk are conflicting. In this study, we investigated NQO1genotype in relation to lung cancer risk. The cases were patients attending Chest diseases unit in the Alexandria Main University Hospital with bronchogenic carcinoma in different stages. The control group consisted of age-matched male adults from the same socioeconomic class. DNA extraction from EDTA blood samples and genotyping was successfully carried out for 100 cases and 100 controls by PCR-RFLP and PCR-CTPP. Pat – ients carrying at least one variant allele for the NQO1 609 SNP (CT/TT genotype) were found to have almost a 2.2 -fold increased lung cancer risk than those with CC genotype, 4.3- fold increased risk of developing SCLC and 3.8- fold increased risk for lung cancer with other histological type. Furthermore, the heavy smokers (>21 p-y) patients with one or two copies of the T variant allele had 3.6-fold increased lung cancer risk compared to those with CC genotype, while, the risk for squamous cell carcinoma was 2.4-fold and 17.9-fold for SCLC. These results suggest that individuals with reduced enzyme activity, due to NQO1 609 C˃T polymorphism, may therefore have an increased risk of lung cancer.
