Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively).... In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.
Keywords:
Alpha-1-antitrypsin / Neutrophil elastase / Polymorphisms / Lung cancer
TY - JOUR
AU - Topić, Aleksandra
AU - Ljujić, Mila
AU - Nikolić, Aleksandra
AU - Petrović-Stanojević, Nataša
AU - Dopuđa-Pantić, Vesna
AU - Mitić-Milikić, Marija
AU - Radojković, Dragica
PY - 2011
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1547
AB - Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.
PB - Springer, Dordrecht
T2 - Pathology & Oncology Research
T1 - Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer
VL - 17
IS - 1
SP - 75
EP - 80
DO - 10.1007/s12253-010-9283-5
ER -
@article{
author = "Topić, Aleksandra and Ljujić, Mila and Nikolić, Aleksandra and Petrović-Stanojević, Nataša and Dopuđa-Pantić, Vesna and Mitić-Milikić, Marija and Radojković, Dragica",
year = "2011",
abstract = "Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.",
publisher = "Springer, Dordrecht",
journal = "Pathology & Oncology Research",
title = "Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer",
volume = "17",
number = "1",
pages = "75-80",
doi = "10.1007/s12253-010-9283-5"
}
Topić, A., Ljujić, M., Nikolić, A., Petrović-Stanojević, N., Dopuđa-Pantić, V., Mitić-Milikić, M.,& Radojković, D.. (2011). Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer. in Pathology & Oncology Research
Springer, Dordrecht., 17(1), 75-80.
https://doi.org/10.1007/s12253-010-9283-5
Topić A, Ljujić M, Nikolić A, Petrović-Stanojević N, Dopuđa-Pantić V, Mitić-Milikić M, Radojković D. Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer. in Pathology & Oncology Research. 2011;17(1):75-80.
doi:10.1007/s12253-010-9283-5 .
