Lesley McGuffog
A5102854004- Ovarian cancer diagnosis and treatment
- BRCA gene mutations in cancer
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Nutrition, Genetics, and Disease
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- interferon and immune responses
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Cancer-related molecular mechanisms research
- Genetic and phenotypic traits in livestock
- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
- Genomics and Rare Diseases
- Male Breast Health Studies
- RNA and protein synthesis mechanisms
- Evolution and Genetic Dynamics
- Genetic Syndromes and Imprinting
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Genetically Modified Organisms Research
University of Cambridge
2006-2022
MRC Epidemiology Unit
2006-2011
Cancer Research UK
2005-2010
Institute of Cancer Research
2010
Centre hospitalier universitaire de Québec
2010
Université Laval
2010
University of Cologne
2010
University of Birmingham
2005
Homozygous or compound heterozygous mutations in the ATM gene are principal cause of ataxia telangiectasia (A-T). Several studies have suggested that carriers at increased risk breast cancer and perhaps other cancers, but precise is uncertain.Cancer incidence mortality information for 1160 relatives 169 UK A-T patients (including 247 obligate carriers) was obtained through National Health Service Central Registry. Relative risks (RRs) carriers, allowing genotype uncertainty, were estimated...
Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 ovarian (OC) risk. Several of these are also BC or OC for women who carry a pathogenic mutation in the high-risk genes BRCA1 BRCA2. The combined effects variants on BRCA2 carriers not yet been assessed while their clinical management could benefit from improved personalized estimates. We constructed polygenic scores (PRS) using susceptibility...
To provide precise age-specific risk estimates of cancers other than female breast and ovarian associated with pathogenic variants (PVs) in
Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) that are independently associated with small increments in risk of prostate cancer, opening up the possibility for using such variants prediction. Using segregation analysis population-based samples 4,390 families cancer patients from UK and Australia, assuming all familial aggregation has genetic causes, we previously found best model susceptibility to was a mixed inheritance included both...
A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic variant. We used large-scale genetic clinical resources from the ENIGMA, CIMBA BCAC consortia assess pathogenicity C. The combined odds for causality considering case-control, segregation breast tumor...
Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these modifiers were originally as genetic factors for genome-wide association (GWASs), additional may be from promising signals discovered GWAS. A total of 350 SNPs candidate (P < 1 × 10−3) two GWAS genotyped 3451 2006 carriers nine centers. Associations with assessed using Cox models weighted penetrance. Eight 12 carriers,...
BRCA1 BRCA2 mutational spectrum in the Middle East, North Africa, and Southern Europe is not well characterized. The unique history cultural practices characterizing these regions, often involving consanguinity inbreeding, plausibly led to accumulation of population-specific founder pathogenic sequence variants (PSVs). To determine recurring BRCA PSVs locales, a search PUBMED, EMBASE, BIC, CIMBA was carried out combined with outreach researchers from relevant countries for unpublished data....
BRCA1 and BRCA2 (BRCA1/2) pathogenic sequence variants (PSVs) confer elevated risks of multiple cancers. However, most BRCA1/2 PSVs reports focus on European ancestry individuals. Knowledge the PSV distribution in African descent individuals is poorly understood. We undertook a systematic review published literature publicly available databases reporting also accessed Consortium Investigators Modifiers (CIMBA) database to identify or Using these data, we inferred which BRCA were likely be...
The CHEK2 1100delC protein-truncating mutation has a carrier frequency of approximately 0.7% in Northern and Western European populations confers an 2-fold increased risk breast cancer. It also been suggested to increase risks colorectal prostate cancer, but its involvement with these or other types cancer not confirmed. incidence than 11,116 individuals from 734 non-BRCA1/2 families the United Kingdom, Germany, Netherlands, States was compared that predicted by population rates. Relative...
Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation this with several genetic and non-genetic modifiers identified. The protein plays central role DNA repair, mechanism that particularly instrumental safeguarding cells against tumorigenesis. We hypothesized polymorphisms alter expression and/or function carried on wild-type (non-mutated) copy would modify cancer carriers mutations. A total 9874 mutation were available...
The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate play a key role in the initiation of apoptosis. Suppression apoptosis is one major mechanisms underlying origin progression cancer. Previous case-control studies have indicated that polymorphisms CASP8 D302H CASP10 V410I are associated with reduced risk breast cancer general population.To evaluate whether (CASP10 V410I) modify or ovarian BRCA1 BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects white European...
The TP53 pathway, in which and its negative regulator MDM2 are the central elements, has an important role carcinogenesis, particularly BRCA1- BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) promoter region of (309T>G, rs2279744) a coding SNP (Arg72Pro, rs1042522) have been shown to be functional significance. To investigate whether these SNPs modify breast cancer risk for BRCA1 BRCA2 mutation carriers, we pooled genotype data on Arg72Pro 7011 carriers 309T>G 2222 from...
The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors.To investigate whether common genetic variants modify penetrance for mutation carriers, we undertook a two-staged genome-wide association study in carriers.In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (,40 years) affected and 804 unaffected carriers European ancestry.Associations evaluated survival-based score...
The close functional relationship between p53 and the breast cancer susceptibility genes BRCA1 BRCA2 has promoted investigation of various polymorphisms in gene as possible risk modifiers BRCA1/2 mutation carriers. Specifically, two p53, c.97-147ins16bp p.Arg72Pro have been analysed putative variants, it recently reported that a haplotype combining absence 16-bp insertion presence proline at codon 72 (No Ins-72Pro) was associated with an earlier age onset first primary tumour carriers...
Single-nucleotide polymorphisms (SNPs) in genes involved DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations the high-risk susceptibility BRCA1 and BRCA2. The base excision (BER) pathway could particularly interesting given relation synthetic lethality that exists between one components pathway, PARP1, both In this study, we have evaluated XRCC1 gene participates BER modifier Three common SNPs gene, c.-77C>T (rs3213245) p.Arg280His (rs25489)...
Abstract Germline genetic variation has been suggested to influence the survival of breast cancer patients independently tumor pathology. We have studied associations variants in two etiologically unique groups patients, carriers germline pathogenic BRCA1 or BRCA2 genes. found that rs57025206 was significantly associated with overall survival, predicting higher mortality carrier estrogen receptor-negative cancer, a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10 −9 )....
<div>Abstract<p>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...
<p>Association results after the adjustment for nearby GWAS index SNPs genes with predicted gene expression levels associated ovarian cancer risk at P < 2.21E-6.</p>
<div>Abstract<p>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...
<p>Association results after the adjustment for nearby GWAS index SNPs genes with predicted gene expression levels associated ovarian cancer risk at P < 2.21E-6.</p>
<p>Chromosomal regions with predicted gene expression levels associated epithelial ovarian cancer risk at P < 2.21E-6 either or cross-tissue model.</p>
<p>Online Supplementary Documents</p>