An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for Cp

Large-scale transcriptome-wide association study identifies new prostate cancer risk regions

Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have identified more than 100 risk regions, most of the risk genes at these regions remain largely unknown. Here we integrate the largest PrCa GWAS (N = 142,392) with gene expression measured in 45 tissues (N = 4458), including normal and tumor prostate, to perform a multi-tissue transcriptome-wide association study (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated with PrCa risk, 9 of which are region

Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

Several susceptibility loci for classical Hodgkin lymphoma (cHL) have been reported, however much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies (GWAS), a new GWAS, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all cHL at 6q22.33 (rs9482849, P=1.52 × 10-8) and for nodular sclerosis HL (NSHL) at 3q28 (rs4459895, P=9.43 × 10-17), 6q23.3 (rs6928977, P=4.62 × 10-55 11), 10p14 (rs3781093, P=9.49 × 10-13), 13q34 (rs112998813, P=4.58 × 10-8) and 16p13.13 (rs34972832, P=2.12 × 10-8). Additionally, independent loci within the HLA region are observed for NSHL (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity HL (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.In the United Kingdom, Bloodwise (LLR; 10021) provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the Lymphoma Research Trust is also acknowledged. A.S. is supported by a clinical fellowship from Cancer Research UK. For the UK-GWAS, sample and data acquisition were supported by Breast Cancer Now, the European Union and the Lymphoma Research Trust. The UK-GWAS made use of control genotyping data generated by the WTCCC. For further information, please visit the publishr's website

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

EFEITO ANALGÉSICO DO BUTORFANOL NA DOR SOMÁTICA EM GATOS ANESTESIADOS COM PROPOFOL ANALGESIC EFFECT OF BUTORPHANOL ON SOMATIC PAIN IN CATS ANESTHETIZED WITH PROPOFOL

O propofol é um agente anestésico intravenoso usado para indução e manutenção da anestesia, mas produz analgesia limitada, havendo a necessidade do uso concomitante de analgésicos. Avaliou-se o efeito analgésico do butorfanol na dor somática em gatos anestesiados com doses fracionadas de propofol. Foram utilizados 16 animais, distribuídos aleatoriamente em dois grupos. Os animais do grupo controle foram pré-tratados com 0,2mg/kg de acepromazina por via IM e, após 15 minutos, receberam 6mg/kg de propofol por via IV. Os animais do grupo tratamento foram pré-medicados com uma combinação de acepromazina (0,2mg/kg) e butorfanol (0,8mg/kg), administrados na mesma seringa por via IM, e, após 15 minutos, receberam 6mg/kg de propofol por via IV. Em ambos os grupos, a manutenção da anestesia foi feita com administrações de propofol, na dose de 3mg/kg, por via IV, sempre que necessário, durante 60 minutos. A necessidade de readministração de propofol foi verificada pela resposta apresentada ao pinçamento cutâneo, através de uma pinça de Kocher. Avaliaram-se também as freqüências cardíaca e respiratória, pressão arterial média, saturação de oxiemoglobina e temperatura retal. A administração de butorfanol causou apenas redução nas freqüências cardíaca e respiratória e na saturação de oxiemoglobina, em comparação com o grupo controle,sem exercer influência significativa sobre o período hábil, a dose total administrada e o período de recuperação do propofol. Concluiu-se que a adição de butorfanol não produziu analgesia somática em gatos anestesiados com doses fracionadas de propofol.<br>Propofol is an intravenous anesthetic agent used for induction and maintenance of anesthesia but produces limited analgesia, and concomitant use of analgesics is necessary. The analgesic effect of butorphanol in somatic pain in cats anesthetized with intermittent doses of propofol was evaluated. Sixteen animals were randomly assigned to 2 groups. Control group animals were premedicated with IM acepromazine (0,2mg/kg) and after 15 minutes IV propofol (6mg/kg) was administered. Treatment group animals were premedicated with IM acepromazine (0,2mg/kg) and butorphanol (0,8mg/kg), mixed in the same syringe and after 15 minutes IV propofol (6mg/kg) was administered. In both groups anesthesia was maintained with repeated injections of propofol (3mg/kg) as needed, during 60 minutes. The need to complement propofol doses was determined by reactions to a skin pinch with a Kocher hemostatic forceps.Heart rate, respiratory rate, mean blood pressure, rectal body temperature and oxyhemoglobin saturation were also recorded. Administration of butorphanol caused minimal changes in cardiopulmonary variables compared to control group and did not affect duration of anesthesia and total dose of propofol or recovery period. We concluded that addition of butorphanol did not produce somatic analgesia during anesthesia maintained with repeated injections of propofol in cats

Genome-wide association study of prostate cancer-specific survival

Free to read\ud \ud BACKGROUND: \ud \ud Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.\ud \ud METHODS: \ud \ud We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).\ud \ud RESULTS: \ud \ud We observed no significant association between genetic variants and prostate cancer survival.\ud \ud CONCLUSIONS: \ud \ud Common genetic variants with large impact on prostate cancer survival were not observed in this study.\ud \ud IMPACT: \ud \ud Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes