Polymorphism of alpha-1-antitrypsin in hematological malignancies

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant

Long Term Consequences of the Chernobyl Radioactive Fallout: an Exploration of the Aggregate Data

Context This study investigates the association between the radioactive 137Cesium fallout originated by the 1986 Chernobyl nuclear accident and dispersed over Western Europe, as a result of a combination of radioactive cloud passage days and rainy days over a 10\u2010day period, and long\u2010term health patterns and related costs. Since the half\u2010life of 137Cesium is 30.17 years, part of the radioactivity in the affected regions is still present today, and it is usually still detected in the food chain, although at lower concentration levels. Methods We match longitudinal data on neoplasm incidence over the time span 2000\u20102013 in a number of European regions not immediately adjacent to Chernobyl with the randomly distributed levels of cesium deposition after the nuclear disaster in order to assess whether we can detect an association with the long\u2010term health effects on the European population through a random effects model. Findings Considering 3 levels of fallout deposition\u2014low, medium, and high\u2014hospital discharges after treatment for neoplasms are, respectively, 0.36, 0.44, and 0.98 discharges over 100 inhabitants higher compared to regions with no fallout, with the population average being around 1.7 hospital discharges by neoplasms over 100 inhabitants. We checked the robustness of our findings to a number of tests including a placebo simulation and different model specifications. Conclusions Radioactive fallout is positively associated with a higher incidence of hospital discharges after treatment for neoplasms almost 30 years after its release, with larger effects in regions where the radioactivity was more intense. Our estimates are comparable to the findings of the largest\u2010scale study on the long\u2010term health effects of continuous low levels of radiation exposure among workers in the nuclear industry and suggest that more research is needed on this topic, given its enormous importance for public health and safety