Polymorphisms in the promoter region of neutrophil elastase gene and lung cancer risk

The neutrophil elastase (NE) gene encodes a powerful serine protease that is involved in the process of normal tissue turnover, natural host defense or tissue damage in acute and chronic inflammatory disorders. Furthermore, NE was suggested as one of the determinant factors of individual susceptibility to lung cancer resulting from imbalance between α1-antitrypsin (AT) and NE. To determine whether NE plays a role in risk for lung cancer, we screened polymorphisms in the promoter region of the NE gene and assessed the role of the NE polymorphisms in the risk for lung cancer. We confirmed three previously identified polymorphisms which are located at −903, −741, and extra 52 bp STS relative to the transcription initiation site. In addition, two new polymorphisms at −832 (G/T) and −789 (C/T) were identified. Their rare allelic frequencies of new polymorphism are 0.02 and 0.01, respectively, among Caucasians. The prevalence of the NE −903 (T/T) and (T/G) genotypes were 0.88 and 0.12 in controls as compared to 0.96 and 0.04 in lung cancer patients using genomic DNA isolated from 113 Caucasian lung cancer cases and 131 controls. A significant increase in lung cancer risk was observed for expected high NE activity genotypes (OR = 3.2, 95% CI = 1.02-10.3) as compared to low NE activity genotypes. These results were consistent with previous in vitro functional analysis, which reported an approximately two-fold increase enzyme expression with the −903T/−741G allele as compared to the −903G/−741A variant. These results confirm that the NE promoter region polymorphisms may influence in risk for lung cancer.