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Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer

  • Published:
Pathology & Oncology Research

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.

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Acknowledgments

This work was supported by grants 145036 and 143051 from the Ministry of Science and Environmental Protection, Republic of Serbia.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

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Authors and Affiliations

  1. Institute of Medical Biochemistry, Faculty of Pharmacy, Belgrade University, Vojvode Stepe 450, 11221, Belgrade, Serbia

    Aleksandra Topic

  2. Institute of Molecular Genetics and Genetic Engineering, Belgrade University, Belgrade, Serbia

    Mila Ljujic, Aleksandra Nikolic & Dragica Radojkovic

  3. Zvezdara University Medical Center, Belgrade, Serbia

    Natasa Petrovic-Stanojevic & Vesna Dopudja-Pantic

  4. Institute for Lung Disease and TB, University Clinical Center of Serbia, Belgrade, Serbia

    Marija Mitic-Milikic

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  1. Aleksandra Topic
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  2. Mila Ljujic
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Correspondence to Aleksandra Topic.

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Topic, A., Ljujic, M., Nikolic, A. et al. Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer. Pathol. Oncol. Res. 17, 75–80 (2011). https://doi.org/10.1007/s12253-010-9283-5

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  • DOI: https://doi.org/10.1007/s12253-010-9283-5

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