Hypoxia-inducible factor-1α gene polymorphisms and cancer risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The results from the published studies on the association between <it>hypoxia-inducible factor -1α </it>(HIF-1α) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between <it>HIF-1α </it>1772 C/T and 1790 G/A polymorphisms and cancer.</p> <p>Methods</p> <p>The meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and genotypic comparisons between cases and controls were evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also performed. We included prostate cancer in male subgroup, and female specific cancers in female subgroup.</p> <p>Results</p> <p>For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01, 1.65)], P = 0.04, P_{heterogeneity}< 0.00001, and OR = 2.18 [95% CI (1.32, 3.62)], P = 0.003, P_{heterogeneity}= 0.02, respectively. The effect of the genotype TT on cancer especially exists in Caucasians and female subjects: OR = 2.40 [95% CI (1.26, 4.59)], P = 0.008, P_{heterogeneity}= 0.02, and OR = 3.60 [95% CI (1.17, 11.11)], P = 0.03, P_{heterogeneity}= 0.02, respectively. For the 1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and dominant model comparison suggested a significant association of 1790 G/A polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08, 0.90)], P = 0.03, P_{heterogeneity}= 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P = 0.04, P_{heterogeneity}= 0.41, respectively. The frequency of the <it>HIF-1α </it>1790 A allele was very low and only two studies were included in the breast cancer subgroup.</p> <p>Conclusions</p> <p>Our meta-analysis suggests that the <it>HIF-1α </it>1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance.</p

Nighttime lights, urban features, household poverty, depression, and obesity

Nighttime Light Emission (NLE) is associated with diminished mental and physical health. The present study examines how NLE and associated urban features (e.g., air pollution, low green space) impact mental and physical wellbeing. We included 200,393 UK Biobank Cohort participants with complete data. The study was carried out in two steps. In Step1, we assessed the relationship between NLE, deprivation, pollution, green space, household poverty and mental and physical symptoms. In Step2, we examined the role of NLE on environment-symptom networks. We stratified participants into high and low NLE and used gaussian graphical model to identify nodes which bridged urban features and mental and physical health problems. We then compared the global strength of these networks in high vs low NLE. We found that higher NLE associated with higher air pollution, less green space, higher economic and neighborhood deprivation, higher household poverty and higher depressed mood, higher tiredness/lethargy and obesity (R-training_mean = 0.2624, P-training_mean < .001; R-test_mean = 0.2619, P-test_mean < .001). We also found that the interaction between environmental risk factors and mental, physical problems (overall network connectivity) was higher in the high NLE network than in the low NLE network (t = 0.7896, P < .001). In areas with high NLE, economic deprivation, household poverty and waist circumference acted as bridge factors between the key urban features and mental health symptoms. In conclusion, NLE, urban features, household poverty and mental and physical symptoms are all interrelated. In areas with high NLE, urban features associate with mental and physical health problems at a greater magnitude than in areas with low NLE

Low energy ion backscattering spectrometry of multi-layer targets. - Energy loss and straggling of H and He ions of keV energies in Si and C

SIGLEAvailable from FIZ Karlsruhe / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Role of polygenic and environmental factors in the co-occurrence of depression and psychosis symptoms:a network analysis

Depression and psychosis are often comorbid; they also have overlapping genetic and environmental risk factors, including trauma and area-level exposures. The present study aimed to advance understanding of this comorbidity via a network approach, by (1) identifying bridge nodes that connect clusters of lifetime depression and psychosis symptoms and (2) evaluating the influence of polygenic and environmental risk factors in these symptoms. This study included data from European ancestry participants in UK Biobank, a large population-based sample (N = 77,650). In Step 1, a network model identified bridge nodes between lifetime symptoms of depression and psychosis and functional impairment. In Step 2, genetic and environmental risk factors were incorporated to examine the degree to which symptoms associated with polygenic risk scores for depression and schizophrenia, lifetime exposure to trauma and area-level factors (including deprivation, air pollution and greenspace). Feelings of worthlessness, beliefs in unreal conspiracy against oneself, depression impairment and psychosis impairment emerged as bridges between depression and psychosis symptoms. Polygenic risk scores for depression and schizophrenia were predominantly linked with depression and psychosis impairment, respectively, rather than with specific symptoms. Cumulative trauma emerged as a bridge node associating deprivation with feelings of worthlessness and beliefs in unreal conspiracy, indicating that the experience of trauma is prominently linked with the co-occurrence of depression and psychosis symptoms related to negative views of oneself and others. These key symptoms and risk factors provide insights into the lifetime co-occurrence of depression and psychosis

Calculation of energy-loss straggling of C, Al, Si, and Cu for fast H, He, and Li ions

We present theoretical calculations of the energy-loss straggling of C, Al, Si, and Cu targets for H, He, and Li ions in the range of intermediate to high energies (0.01–10 MeV∕u). These calculations have been done by employing the dielectric formalism and by considering the different equilibrium charge states of the swift ion inside the solid as a function of its energy. Two different models are used: the Mermin energy-loss functions combined with generalized oscillator strengths (MELF-GOS) and the shellwise application of the local plasma approximation (SLPA). The MELF-GOS describes the target outer-electron excitations through a fitting to experimental data in the optical limit, employing a linear combination of Mermin-type energy-loss functions; the excitations of the inner-shell electrons are taken into account by means of generalized oscillator strengths. The SLPA employs a free-electron-gas model for the target valence electrons and the local density approximation for each shell of target electrons separately by using Hartree-Fock atomic wave functions. The results of the energy-loss straggling obtained by the two independent models show good agreement with the available experimental data. The calculated energy-loss straggling tends at high energies to the Bohr value and takes values below it at intermediate energies. The Bethe-Livingston shoulder (or overshooting) at intermediate energies does not appear in the present calculations. We find that the energy-loss straggling normalized to ZP2 is almost independent of the ion atomic number ZP; therefore, the results for H, He, and Li projectiles in each target can be approximated by a universal curve at high energies.This work was supported by the Spanish Ministerio de Educación y Ciencia (Projects Nos. BFM2003-04457-C02-01 and BFM2003-04457-C02-02), by the Universidad de Buenos Aires (Project UBACyT), the Argentinian Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and the Agencia Nacional de Promoción Científica y Tecnológica of Argentina (ANPCyT). S.H.A. thanks Fundación Cajamurcia for a postdoctoral grant

Diversity and function of motile ciliated cell types within ependymal lineages of the zebrafish brain

10.1016/j.celrep.2021.109775Cell Reports37110977

An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1 alpha) Polymorphisms and Osteonecrosis

Bone hypoxia resulting from impaired blood flow is the final pathway for the development of osteonecrosis (ON). The aim of this study was to evaluate if HIF-1 alpha, the major transcription factor triggered by hypoxia, is genetically implicated in susceptibility to ON. For this we analyzed frequencies of three known HIF-1 alpha polymorphisms: one in exon 2 (C111A) and two in exon 12 (C1772T and G1790A) and their association with ON in a Greek population. Genotype analysis was performed using PCR-RFLP and rare alleles were further confirmed with sequencing. We found that genotype and allele frequency of C1772T and G1790A SNP of HIF-1 alpha (SNPs found in our cohort) were not significantly different in ON patients compared to control patients. Furthermore these SNPs could not be associated with the different subgroups of ON. At the protein level we observed that the corresponding mutations (P582S and A588T, respectively) are not significant for protein function since the activity, expression and localization of the mutant proteins is practically indistinguishable from wt in HEK293 and Saos-2 cells. These results suggest that these missense mutations in the HIF-1 alpha gene are not important for the risk of developing ON