Daniel R. Barnes
A5054396870- Genetic Associations and Epidemiology
- BRCA gene mutations in cancer
- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- Nutrition, Genetics, and Disease
- Bioinformatics and Genomic Networks
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- PARP inhibition in cancer therapy
- Pancreatic function and diabetes
- Smoking Behavior and Cessation
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Folklore, Mythology, and Literature Studies
- Chemotherapy-induced cardiotoxicity and mitigation
- American Literature and Humor Studies
University of Cambridge
2014-2024
FirstHealth of the Carolinas
2021
University Hospitals of Leicester NHS Trust
2021
Glenfield Hospital
2021
General Motors (Poland)
2020
United States Air Force
2020
Medical Research Council
2011-2013
MRC Epidemiology Unit
2011-2012
Addenbrooke's Hospital
2011-2012
The Ohio State University
1973
<h3>Importance</h3> The clinical management of<i>BRCA1</i>and<i>BRCA2</i>mutation carriers requires accurate, prospective cancer risk estimates. <h3>Objectives</h3> To estimate age-specific risks of breast, ovarian, and contralateral breast for mutation to evaluate modification by family history location. <h3>Design, Setting, Participants</h3> Prospective cohort study 6036<i>BRCA1</i>and 3820<i>BRCA2</i>female (5046 unaffected 4810 with or ovarian both at baseline) recruited in 1997-2011...
OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, resistance, type 2 diabetes (T2D). Studies the processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted meta-analysis genome-wide association tests ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) fasting in 10,701 nondiabetic adults...
Background Germline pathogenic variants in SDHB/SDHC / SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management mutation carriers. We estimate for symptomatic tumours elucidate genotype–phenotype correlations a large cohort Methods A retrospective survey 1832 individuals referred genetic testing due to personal or family history phaeochromocytoma/paraganglioma. 876...
Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing thirty-three individuals from 15 to identify potential predisposing genes. Our analysis identified heterozygous, deleterious mutations in DNA repair genes FANCC BLM, which are responsible autosomal recessive disorders Fanconi Anemia Bloom syndrome. total, screening...
Abstract Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood spleen. Using expression quantitative trait loci (eQTL) reported these identify 26 previously unreported, likely target genes of overall risk variants, 17 for estrogen receptor (ER)-negative cancer, several with a known function. We...
Abstract Quantifying the genetic correlation between cancers can provide important insights into mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six types based on a total of 296,215 cases and 301,319 controls European ancestry, here we estimate pair-wise correlations breast, colorectal, head/neck, lung, ovary prostate cancer, 38 other diseases. We observed statistically significant lung head/neck ( r g = 0.57, p 4.6 × 10 −8 ), breast ovarian...
We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with risks BRCA1 and BRCA2 pathogenic variant carriers. Retrospective cohort data on 18,935 12,339 female carriers of European ancestry were available. Three versions a 313 single-nucleotide polymorphism (SNP) BC PRS evaluated based whether they predict overall, estrogen receptor (ER)-negative, ER-positive BC, two overall high-grade serous EOC. Associations...
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could predictive performance over standard approaches PRS construction. Here, we implemented computationally efficient, penalized, logistic regression (lasso, elastic net, stepwise) individual level genotype data and a Bayesian framework with continuous shrinkage, "select shrink summary statistics" (S4),...
Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide study to search for novel genetic plausible at known GWAS loci. We used RNA sequencing data (68 normal tissue samples from 68 individuals 6,124...
The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early detection risk reduction this population.
Germline mutations in BRCA1 and BRCA2 (BRCA1/2) genes considerably increase breast ovarian cancer risk. Given that tumors with these have elevated genomic instability, they exhibit relative vulnerability to certain chemotherapies targeted treatments based on poly (ADP-ribose) polymerase (PARP) inhibition. However, the molecular mechanisms influence risk therapeutic benefit or resistance remain only partially understood. also been implicated suppression of R-loops, triple-stranded nucleic...
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs BRCA1/2 were overall cancer high grade (Gleason 8+) using an international sample 65 171 male PSV carriers cancer, 3,388 2,880 without the 3′ region (c.7914+) significantly elevated compared reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P 0.001], as well Gleason 8+ (HR 3.11; CI, 1.63–5.95;...
Abstract Previous transcriptome‐wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome‐wide (GWAS), but analyses of subtype‐specific associations been limited. In this study, we conducted a TWAS using gene GTEx summary statistics the hitherto largest GWAS meta‐analysis for overall, estrogen receptor subtypes (ER+ ER−). We further compared with ER+ ER− subtypes, case‐only approach. also multigene conditional in...
Background Carriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk developing breast ovarian cancer than general population. It is unclear if these PVs influence other or factors, including age menopause (ANM), menarche (AAM), menstrual cycle length, BMI height. There a biological rationale for associations between reproductive anthropomorphic traits, example involving DNA damage repair mechanisms. The evidence against such limited. Methods We used data...