Julian Barwell
A5064934892- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Nutrition, Genetics, and Disease
- Genetic factors in colorectal cancer
- Genomics and Rare Diseases
- DNA Repair Mechanisms
- Genomic variations and chromosomal abnormalities
- Genetics, Bioinformatics, and Biomedical Research
- Prostate Cancer Treatment and Research
- Adrenal and Paraganglionic Tumors
- Prostate Cancer Diagnosis and Treatment
- Pituitary Gland Disorders and Treatments
- CRISPR and Genetic Engineering
- Aortic aneurysm repair treatments
- Cancer, Hypoxia, and Metabolism
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Health, Environment, Cognitive Aging
- Hormonal Regulation and Hypertension
- Liver Disease Diagnosis and Treatment
- Aortic Disease and Treatment Approaches
- PARP inhibition in cancer therapy
- Global Cancer Incidence and Screening
- Cancer-related Molecular Pathways
- Health disparities and outcomes
James Paget University Hospital
2025
University of Leicester
2014-2024
University Hospitals of Leicester NHS Trust
2014-2024
St George's Hospital
2006-2023
National Health Service
2011-2022
Leicester Royal Infirmary
2012-2022
Imperial College London
2021
University of Leeds
2021
Royal Brompton & Harefield NHS Foundation Trust
2021
MRC London Institute of Medical Sciences
2021
Reliable estimates of cancer risk are critical for guiding management BRCA1 and BRCA2 mutation carriers. The aims this study were to derive penetrance breast cancer, ovarian contralateral in a prospective series carriers assess how these risks modified by common susceptibility alleles. Prospective estimated using cohort 978 909 from the United Kingdom. Nine hundred eighty-eight women had no or diagnosis at baseline, 1509 unaffected 651 been diagnosed with unilateral cancer. Cumulative...
The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDHB, -C -D), act as tumour suppressors. Germline mutations in FH predispose individuals to leiomyomas renal cell cancer (HLRCC), whereas SDH cause paragangliomas phaeochromocytomas (HPGL). In this study, we have shown that FH-deficient cells tumours accumulate and, a lesser extent, succinate. SDH-deficient principally situ analyses showed these also over-expression of hypoxia-inducible factor 1α...
PURPOSE To estimate age-specific relative and absolute cancer risks of breast to ovarian, pancreatic, male breast, prostate, colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these have not been extensively characterized. METHODS We analyzed data from 524 families PVs 21 countries. Complex segregation analysis was used (RRs; country-specific population incidences) cancers. The models allowed for residual familial aggregation ovarian were adjusted the...
Abstract Introduction It is frequent for news items to lead a short lived temporary increase in interest particular health related service, however it rare this have long lasting effect. In 2013, the UK particular, there has been unprecedented publicity hereditary breast cancer, with Angelina Jolie’s decision genetic testing BRCA1 gene and subsequently undergo risk reducing mastectomy (RRM), pre-release of NICE guidelines on familial cancer January their final release 26 th June. The created...
Men with germline breast cancer 1, early onset (BRCA1) or 2, (BRCA2) gene mutations have a higher risk of developing prostate (PCa) than noncarriers. IMPACT (Identification genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium 62 centres 20 countries evaluating the use targeted PCa men mutations.
Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) men with germline BRCA1/2 mutations.
BRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of estimates reported that are based on retrospective studies. To estimate relative absolute PCa risks BRCA1/2 to assess modification by age, family history, mutation location. This was prospective cohort study male (n = 376) carriers 447) identified in clinical genetics centres the UK Ireland (median follow-up 5.9 5.3 yr, respectively). Standardised incidence/mortality ratios (SIRs/SMRs)...
Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease. To determine the mutational status FIPA and young patients, analyzing their clinical characteristics, perform AIPmut carrier family members. This was observational, longitudinal study conducted...
Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these different subtypes in and carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 7,080 carriers, whom 4,310 had been affected information either ER PR tumour, assess associations 12 loci tumour...
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...
Lynch syndrome is a rare familial cancer caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging increase risk of early-onset aggressive prostate The IMPACT study prospectively assessing prostate-specific antigen (PSA) screening men with germline variants. Here, we report usefulness PSA screening, incidence, tumour characteristics after first round...
Abstract Context: Activation of the hypoxia-inducible transcription factors HIF-1 and HIF-2 a HIF-independent defect in developmental apoptosis have been implicated pathogenesis pheochromocytoma (PCC) associated with VHL, SDHB, SDHD mutations. Objective: Our objective was to compare protein (HIF-1α, EPAS1, JunB, CCND1, CD34, CLU) gene (VEGF, BNIP3) expression patterns VHL SDHB/D tumors. Results: Overexpression relatively more common than PCC (12 13 vs. 14 20, P = 0.02), whereas nuclear...
Ethnic disparities in use of cancer genetics services raise concerns about equitable opportunity to benefit from familial risk assessment, improved survival and quality life. This paper considers available research explore what may hinder or facilitate minority ethnic access services. We sought inform service development for people South Asian, African Irish origin at breast, ovarian, colorectal prostate cancers the UK. Relevant studies UK, North America Australasia were identified six...
Abstract Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting to clinical characteristics AIPmut AIPneg patients. Design 12-year prospective, observational study. Participants & Setting We studied probands...
Abstract Background Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation NF2-related schwannomatosis patients associated with increased rates subsequent (M)/malignant progression (MP). Methods All UK NF2 were eligible if they had a clinical/molecular diagnosis. Cases treated for tumors. Controls matched...
Research studies have reported that about a third of individuals with phaeochromocytoma/paraganglioma (PPGL) an inherited predisposition, although the frequency specific mutations can vary between populations. We evaluated VHL, SDHB and SDHD mutation testing in cohorts patients non-syndromic PPGL head neck paraganglioma (HNPGL).Prospective, observational evaluation NHS practice.Individuals PPGL/HNPGL referred to supraregional genetics service over 10-year period.Clinical (age, tumour site,...