Background Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis. Objectives The aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers. Study design The study included 132 lung cancer patients and 396 controls from northern Poland, matched by sex, age and smoking status. The median cigarette pack-years of smoking among both cases and controls was 30.0. Serum, red blood cell (RBC) folates and serum homocysteine concentrations were measured. The genotypes in selected polymorphic sites of the MTHFR , CBS , SHMT1 , MTHFD1 , MTRR , MTR , TYMS DHFR , TCN2 , and SLC19A1 genes were determined. All study participants underwent scanning with low-dose computed tomography. Results Serum folate concentrations above the median (> 17.5 nmol/l among the healthy controls) were associated with an increased lung cancer risk (odds ratio [OR], 1.54, 95% confidence intervals [CI], 1.04–2.29, P = 0.031). An analogous trend was observed when the population was analysed after subdivision according to RBC folate concentrations, that is, above a value of 506.5 nmol/l (OR, 1.53; 95% CI, 0.95–2.47; P = 0.084). Additionally, in a subset of women, an increased risk of lung cancer development was associated with the SLC19A1 c.80AA genotype (c.80AA versus GG OR, 3.14; 95% CI, 1.32–7.46; P = P = 0.010). Conclusion These results suggest that, in the population consisting of heavy smokers, high folate levels add to the cancerogenic effect of smoking.
BackgroundThe neonatal murine heart is able to regenerate after severe injury; this capacity however, quickly diminishes and it is lost within the first week of life. DNA methylation is an epigenetic mechanism which plays a crucial role in development and gene expression regulation. Under investigation here are the changes in DNA methylation and gene expression patterns which accompany the loss of regenerative potential.ResultsThe MeDIP-chip (methylated DNA immunoprecipitation microarray) approach was used in order to compare global DNA methylation profiles in whole murine hearts at day 1, 7, 14 and 56 complemented with microarray transcriptome profiling. We found that the methylome transition from day 1 to day 7 is characterized by the excess of genomic regions which gain over those that lose DNA methylation. A number of these changes were retained until adulthood. The promoter genomic regions exhibiting increased DNA methylation at day 7 as compared to day 1 are significantly enriched in the genes critical for heart maturation and muscle development. Also, the promoter genomic regions showing an increase in DNA methylation at day 7 relative to day 1 are significantly enriched with a number of transcription factors binding motifs including those of Mfsd6l, Mef2c, Meis3, Tead4, and Runx1.ConclusionsThe results indicate that the extensive alterations in DNA methylation patterns along the development of neonatal murine hearts are likely to contribute to the decline of regenerative capabilities observed shortly after birth. This conclusion is supported by the evidence that an increase in DNA methylation in the neonatal murine heart from day 1 to day 7 occurs in the promoter regions of genes playing important roles in cardiovascular system development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2545-1) contains supplementary material, which is available to authorized users.
This work presents the influence of atmospheric circulation on the occurrence of dry and wet periods in the central Polish region of Kujawy. The material on which the authors relied encompassed monthly totals of precipitation obtained from 10 weather stations in the period 1954–2018. Both dry and wet periods have been identified on the basis of monthly values of the Standardised Precipitation Index (SPI). Additionally, the calendar of circulation types over Central Poland was used to determine the atmospheric circulation indices: western (W), southern (S) and cyclonicity (C). The analyses have indicated that the region concerned experiences low precipitation totals in comparison with the rest of Poland. According to the circulation indices W, S and C, for Central Poland, the air mass advection from the West prevails over that from the East. Moreover, a slightly more frequent inflow of air from the South than from the North has been observed. The frequency of anticyclonic situations is higher than that of the cyclonic types in this part of Europe. Drought spells occurred in the study area at a clear dominance of anticyclonic circulation, with the inflow of air mostly from the North and with increased westerly circulation. On the other hand, the occurrence of wet periods was mainly influenced by cyclonic circulation during the advection of the masses from the South and West. Dry and wet periods accounted for 28% and 27% of the study period, respectively.
Oxidative stress is believed to play a critical role in atherosclerosis initiation and progression. In line with this, in a group of 1099 subjects, we determined eight single nucleotide polymorphisms (SNPs) related to oxidative stress (PON1 c.575A>G, MPO c.−463G>A, SOD2 c.47T>C, GCLM c.−590C>T, NOS3 c.894G>T, NOS3 c.−786T>C, CYBA c.214C>T, and CYBA c.−932A>G) and assessed the extent of atherosclerosis in coronary arteries based on Gensini score. An increased risk of having a Gensini score in the higher half of the distribution was observed for the PON1 c.575G allele (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.004–1.617, p = 0.046). Next, the genetic risk score (GRS) for the additive effect of the total number of pro-oxidative alleles was assessed. We noted an increase in the risk of having a Gensini score above the median with the maximum number of risk alleles (OR = 2.47, 95% CI: 1.19–5.23, p = 0.014). A univariate Spearman’s test revealed significant correlation between the total number of pro-oxidant alleles (GRS) and the Gensini score (ρ = 0.068, p = 0.03). In conclusion, the PON1 c.575A>G variant and the high number of risk alleles (GRS) were independent risk factors for a high Gensini score. We suggest, however, that GRS might occur as a more valuable component in adding a predictive value to the genetic background of atherosclerosis.
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