RESUMO
PURPOSE: Alpha-1-antitrypsin (AAT) as the major circulating inhibitor of proteases has important role in protease-antiprotease homeostasis. Recent studies have confirmed its antiapoptotic role. AAT is a highly polymorphic protein. Individuals with normal variants have normal serum levels and functional activity of ATT. However, individuals with hereditary AAT deficiency (AATD) have low circulating levels of AAT. Severe AATD was identified as genetic risk factor for early onset of pulmonary emphysema. Association between AAT phenotypes and lung cancer (LC) is not clear, and different studies show contradictory results. The aim of this case-control study was to investigate phenotypes and serum level of AAT in LC. METHODS: The study group included 147 patients with LC, classified as small cell lung cancer (SCLC, n=42) and non-small cell lung cancer (NSCLC, n=105). The control group consisted of 273 healthy blood donors. AAT phenotyping was performed by isoelectric-focusing and AAT concentration was measured using nephelometry. RESULTS: There were no differences in the frequencies of AAT phenotypes and alleles between the control group and LC patients, as well as between NSCLC and SCLC groups. An elevated level of AAT was obtained in LC patients. PiMZ and PiMS phenotypes in LC patients were not deficient in the classical sense. AAT levels were 90 and 134%, respectively, when compared to PiMM phenotype in the control group. CONCLUSION: Our findings revealed that moderate deficiency of AAT is not risk factor for LC development. Although polymorphism of AAT was not associated with risk of LC, further research of this antiprotease and antiapoptotic protein could clarify its role in carcinogenesis, given its high concentration in LC patients, even in AATD patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Deficiência de alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético , Carcinoma de Pequenas Células do Pulmão/genética , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are a major cause of morbidity and mortality worldwide. In both diseases airways inflammation plays an important role. Functional promoter polymorphism, at the position -308, of tumor necrosis factor (TNF)-alpha represents attractive potential susceptibilty marker for both diseases. In order to investigate the role of this polymorphism in COPD and LC, a case-control study was performed. The patient groups consisted of 97 subjects with COPD and 70 subjects with LC, while the control group encompassed 102 subjects. Results of our study showed significant decrease of heterozygote for TNF-alpha-308 1/2 gene variant in COPD group in comparison to controls (p=0.043). According to our results heterozygous carriers of TNF-alpha-308 1/2 polymorphism had a2.3-fold decreased risk for COPD development (OR=0.44, 95%CI=0.20-0.97). In patients with lung cancer we also observed a trend of decreased distribution of TNF-alpha-308 1/2 heterozygotes, but statistical significance was not achieved. To our knowledge, this is the first study implicating decreased frequency of TNF-alpha-308 1/2 gene variant in patients with COPD and LC. Although these results need to be confirmed on larger cohort, they represent anew and interesting finding, not reported in other populations tested so far.
