The allelic frequency for S and Z mutations in the SERPINA1 gene in NSCLC patients from Poland

Abstract

Background: Alpha-1 antitrypsin (AAT) is encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene cause AAT deficiency (AATD) - a risk factor for a number of chronic lung diseases. The causative link between AATD and non-small cell lung cancer (NSCLC) is still controversial due to insufficient or inconsistent research data. Objective: We evaluated the frequency of the major pathogenic SERPINA1 gene alleles among Polish NSCLC patients. Methods: blood samples were collected from 468 NSCLC patients (ADC, SQC, LCC, NOS, stages I-IV). The serum AAT concentration was measured by nephelometry and the phenotype was analyzed by isoelectric focusing in polyacrylamide gel. The SERPINA1 gene variants were identified by DNA sequencing. The frequency of SERPINA1 gene alleles was estimated by means of Hardy-Weinberg equilibrium. Results: 446 out of 468 (95.2%) NSCLC patients presented normal Pi*MM phenotype. AATD alleles were found in 22 patients. 10 (2.1%) carried Pi*S allele, 10 (2.1%) - Pi*Z allele, and 3 (0.6%) – Pi*F allele. Accordingly, the frequency of major AATD alleles was: Pi*S 10.7/1000 (95%CI: 4.1-17.3) and Pi*Z 10.7/1000 (95%CI: 4.1-17.3). The mean serum AAT concentration in NSCLC patients was 180 mg/dL in Pi*MM individuals and 148 mg/dL in AATD allele carriers. Conclusions: The frequency of Pi*S and Pi*Z alleles in NSCLC patients differ noticeably from the general Polish population (Pi*Z 13.7/1000 and Pi*S 7.6/1000): the frequency of Pi*Z allele is lower whereas the frequency of Pi*S is higher. The NSCLC patients who carry AATD allele do not present reduced AAT concentration in blood as compared to the reference values from population studies. The study is on-going.