Mortality in Italian veterans deployed in Bosnia-Herzegovina and Kosovo.

BACKGROUND AND AIMS: The possible increase of cancer risk in military personnel deployed in Balkans during and after the 1992-1999 wars, mainly related to the depleted uranium, was addressed by several studies on European veterans of those war theatres. This article reports on the results of the mortality study on the Italian cohort of Bosnia and Kosovo veterans (Balkan cohort). METHODS: Mortality rates for the Balkan cohort (71 144 persons) were compared with those of the Italian general population as well as to those of a comparable and unselected control cohort of not deployed military personnel (114 269 persons). Ascertainment of vital status during the period 1995-2008 of all the persons in the two cohorts has been carried out through deterministic record linkage with the national death records database, from information provided by the respective Armed Force General Staff, and through the civil registry offices of the veterans' residence or birth municipalities. RESULTS: The Balkan cohort experienced a mortality rates lower than both the general population (SMR = 0.56; 95% CI 0.51-0.62) and the control group (SMR = 0.88; 95% CI 0.79-0.97). Cancer mortality in the deployed cohort group was half of that from the general population mortality rates (SMR = 0.50; 95% CI 0.40-0.62) and slightly lower if compared with the control group cancer mortality rates (SMR = 0.95; 95% CI 0.77-1.18). CONCLUSION: Balkan veteran cohort did not show any increase in general mortality or in cancer mortality.

Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5'-flanking region: a priming effect on the spreading of active demethylation.

The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5'-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation, with an active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region.