Genome-wide association study of circulating folate one-carbon metabolites.

Experimental, observational, and clinical trials support a critical role of folate one-carbon metabolism (FOCM) in colorectal cancer (CRC) development. In this report, we focus on understanding the relationship between common genetic variants and metabolites of FOCM. We conducted a genome-wide association study of FOCM biomarkers among 1,788 unaffected (without CRC) individuals of European ancestry from the Colon Cancer Family Registry.

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis).

The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.

Background: Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States.

Objective: We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex ( = 200) within these populations.

Methods: Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls).

TGF-β1-p53 cooperativity regulates a profibrotic genomic program in the kidney: molecular mechanisms and clinical implications.

Chronic kidney disease affects >15% of the U.S. population and >850 million individuals worldwide.

Single-Entity Electrochemistry of Nanoemulsion: The Nanostructural Effect on Its Electrochemical Behavior.

New electrochemical approaches have been applied to investigate nanoemulsions (NEs) for their nanostructures and the relevant electrochemical activity by single-entity electrochemistry (SEE). Herein, we make highly monodisperse NEs with ∼40 nm diameter, composed of biocompatible surfactants, castor oil as plasticizers, and ion exchangers. Dynamic light scattering (DLS) measurements with periodically varying surfactant to oil ratios provide us with a structural implication about uneven distributions of incorporating components inside NEs.

Correction to: Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.

Every author has erroneously been assigned to the affiliation "62". The affiliation 62 belongs to the author Graham Casey.

Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL.

The risk for non-Hodgkin lymphoma (NHL) is markedly increased in persons living with human immunodeficiency virus (HIV) infection, and remains elevated in those on anti-retroviral therapy (cART). Both the loss of immunoregulation of Epstein-Barr virus (EBV) infected cells, as well as chronic B-cell activation, are believed to contribute to the genesis of AIDS-related NHL (AIDS-NHL). However, the mechanisms that lead to AIDS-NHL have not been completely defined.

MARK2/Par1b kinase present at centrosomes and retraction fibres corrects spindle off-centring induced by actin disassembly.

Tissue maintenance and development requires a directed plane of cell division. While it is clear that the division plane can be determined by retraction fibres that guide spindle movements, the precise molecular components of retraction fibres that control spindle movements remain unclear. We report MARK2/Par1b kinase as a novel component of actin-rich retraction fibres.

Improvements to the Escalation with Overdose Control design and a comparison with the restricted Continual Reassessment Method.

The Escalation with Overdose Control (EWOC) design for cancer dose finding clinical trials is a variation of the Continual Reassessment Method (CRM) that was proposed to overcome the limitation of the original CRM of exposing patients to high toxic doses. The properties of EWOC have been studied to some extent, but some aspects of the design are not well studied, and its performance is not fully understood. Comparisons of the EWOC design to the most commonly used modified CRM designs have not yet been performed, and the advantages of EWOC over the modified CRM designs are unclear.

A genome-wide association study of prostate cancer in Latinos.

Latinos represent <1% of samples analyzed to date in genome-wide association studies of cancer. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts across populations. In the present study, we performed a GWAS of prostate cancer (PrCa) in 2,820 Latino PrCa cases and 5,293 controls to search for novel PrCa risk loci and to examine the generalizability of known PrCa risk loci in Latino men.

Pericardial Effusion Associated With Sirolimus Use After Renal Transplantation: A Single-Center Case Series.

Pericardial effusion and cardiac tamponade following renal transplantation have been recognized as a potentially serious complications associated with the use of sirolimus for immunosuppression. Our study aims to analyze the development of sirolimus-associated pericardial effusion. Patients who underwent renal transplantation at our institution between 2001 and 2014 were reviewed and the correlation between sirolimus exposure and pericardial effusion was determined.

Translating RB1 predictive value in clinical cancer therapy: Are we there yet?

The retinoblastoma RB1 gene has been identified in the 80s as the first tumor suppressor. RB1 loss of function, as well alterations in its pathway, occur in most human cancers and often have prognostic value. RB1 has a key role in restraining cell cycle entry and, along with its family members, regulates a myriad of cellular processes and affects cell response to a variety of stimuli, ultimately determining cell fate.

Alterations in folate-dependent one-carbon metabolism as colon cell transition from normal to cancerous.

Folate-dependent one-carbon cycle metabolism (FOCM) plays a critical role in maintaining genomic stability through regulating DNA biosynthesis, repair and methylation. Folate metabolites as well as other metabolites in the FOCM are hypothesized to be altered when cells transition from normal to cancerous state. Using cells at different stages in their development into colorectal cancer, the FOCM metabolites were profiled as an effort to phenotype the cells, and the metabolite levels were compared to the expressions of related genes.

Elucidation of causal direction between asthma and obesity: a bi-directional Mendelian randomization study.

Background: Observational associations between asthma and obesity are well established, but inferring causality is challenging. We leveraged publicly available summary statistics to ascertain the causal direction between asthma and obesity via Mendelian randomization in European-ancestry adults.

Methods: We performed two-sample bi-directional Mendelian randomization analysis using publicly available genome-wide association studies summary statistics.

Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation.

Telomeres are repetitive DNA sequences that protect the ends of linear chromosomes, and they are maintained by a ribonucleoprotein complex called telomerase. Variants in genes encoding for telomerase components have been associated with a spectrum of disease in the lung, skin, bone marrow, and liver. Mutations in the telomerase reverse transcriptase and telomerase RNA component genes have been observed at a higher prevalence in patients with liver disease compared with the general population; however, the presence of variants in other components of the telomerase complex and their impact on clinical outcomes has not been explored.

Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis.

Objective: To examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children.

Methods: Forty overweight and obese Hispanic children (8-14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1-3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry.

Correction: Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease.

This article was originally published under the standard License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls.

Germline DNA Repair Gene Mutations in Young-onset Prostate Cancer Cases in the UK: Evidence for a More Extensive Genetic Panel.

Background: Rare germline mutations in DNA repair genes are associated with prostate cancer (PCa) predisposition and prognosis.

Objective: To quantify the frequency of germline DNA repair gene mutations in UK PCa cases and controls, in order to more comprehensively evaluate the contribution of individual genes to overall PCa risk and likelihood of aggressive disease.

Design, Setting, And Participants: We sequenced 167 DNA repair and eight PCa candidate genes in a UK-based cohort of 1281 young-onset PCa cases (diagnosed at ≤60yr) and 1160 selected controls.

Shared heritability and functional enrichment across six solid cancers.

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r = 0.

DNA methylation patterns of adult survivors of adolescent/young adult Hodgkin lymphoma compared to their unaffected monozygotic twin.

DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood ( = 9 pairs, mean age 57.4 y) or saliva ( = 36 pairs, mean age 50.

Author Correction: Germline variation at 8q24 and prostate cancer risk in men of European ancestry.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

A Unified Model for the Analysis of Gene-Environment Interaction.

Gene-environment (G × E) interaction is important for many complex traits. In a case-control study of a disease trait, logistic regression is the standard approach used to model disease as a function of a gene (G), an environmental factor (E), G × E interaction, and adjustment covariates. We propose an alternative model with G as the outcome and show how it provides a unified framework for obtaining results from all of the common G × E tests.

Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.