Christi J. van Asperen
A5042981384- BRCA gene mutations in cancer
- Ovarian cancer diagnosis and treatment
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Nutrition, Genetics, and Disease
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Global Cancer Incidence and Screening
- Genomic variations and chromosomal abnormalities
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- Family Support in Illness
- Genomics and Chromatin Dynamics
- Male Breast Health Studies
- Cancer Risks and Factors
- Prenatal Screening and Diagnostics
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Childhood Cancer Survivors' Quality of Life
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Breast Cancer Treatment Studies
- Ethics in Clinical Research
- Circular RNAs in diseases
Leiden University Medical Center
2015-2024
Leiden University
2012-2023
Cancer Research Center
2015-2021
University of Manchester
2021
St Mary's Hospital
2021
Edinburgh Cancer Research
2021
European Organisation for Research and Treatment of Cancer
2019
Cancer Trials Ireland
2018-2019
Breast International Group
2018-2019
Beatson West of Scotland Cancer Centre
2019
Data for multiple common susceptibility alleles breast cancer may be combined to identify women at different levels of risk. Such stratification could guide preventive and screening strategies. However, empirical evidence genetic risk is lacking. We investigated the value using 77 cancer-associated single nucleotide polymorphisms (SNPs) stratification, in a study 33 673 cases 381 control European origin. tested all possible pair-wise multiplicative interactions constructed 77-SNP polygenic...
A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs risk varied by clinically important tumor characteristics up to 23,039 invasive cases 26,273 controls from 20...
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.
In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival benefit BRRM over BC surveillance has been reported yet. this Dutch multicenter cohort study, we used multivariable Cox models with as a time-dependent covariable to estimate associations between and overall BC-specific mortality rates, separately for BRCA1 BRCA2 carriers. During mean follow-up 10.3 years, 722 out 1712 (42%)...
The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and personal history invasive breast cancer is unknown. We identified cohort 148 female carriers (115 33, respectively) who previously were treated for unilateral stages I-IIIa. In all, 79 underwent CPM, while the other remained under intensive surveillance. mean follow-up was 3.5 years started at time CPM date testing, whichever came last, that is, on average 5 after diagnosis first...
Abstract The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of for BRCA1 or BRCA2 mutation carriers. We evaluated the associations 3 additional single nucleotide (SNPs), rs4973768 SLC4A7/NEK10, rs6504950 STXBP4/COX11, rs10941679 at 5p12, reanalyzed previous using carriers a sample 12,525 7,409 Additionally, we investigated potential interactions between SNPs assessed implications risk prediction. minor alleles were...
Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS two putative candidate genes relation to specific tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) other pathological features. Analyses included up 30 040 invasive cases 53 692 controls from 31 studies within the Cancer Association Consortium. confirmed previous reports...
Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify risks for female carriers mutations. We investigated—for first time to our knowledge—associations common with male BRCA1/ 2 implications prediction. Materials Methods genotyped 1,802 from Consortium Investigators Modifiers by using custom Illumina OncoArray. investigated combined effects established susceptibility on constructing weighted polygenic scores (PRSs) published effect...
Although the benefits of next-generation sequencing (NGS) for diagnosis heterogeneous diseases such as intellectual disability (ID) are undisputed, there is little consensus on relative merits targeted enrichment, whole-exome (WES) or whole-genome (WGS). To answer this question, WES and WGS data from same nine samples were compared, was shown not to miss any variants identified by in a gene panel including ∼500 genes linked ID (500GP). Additionally, deeply sequenced adequately cover ∼99%...
Endometrial cancer (EC) risk in BReast CAncer gene 1/2 (BRCA1/2) mutation carriers is uncertain; therefore, we assessed this a large Dutch nationwide cohort study.
Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks missense these genes uncertain. We analyzed data on 59,639 cases 53,165 controls from studies participating the Breast Cancer Association Consortium BRIDGES project. sampled training (80%) validation (20%) sets to analyze rare ATM (1146 variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), (472). evaluated according five silico prediction-of-deleteriousness algorithms,...
<h3>Aim:</h3> To assess the effectiveness of annual ovarian cancer screening (transvaginal ultrasound and serum CA125 estimation) in reducing mortality from women at increased genetic risk. <h3>Patients methods:</h3> A cohort 3532 risk was screened five European centres between January 1991 March 2007. Survival diagnosis calculated using Kaplan–Meier analysis compared for proven <i>BRCA1/2</i> carriers with non-carriers whether detected prevalence or post-prevalent scan. Screening performed...
Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation disease. To search further genes, we performed combined analysis four genome-wide linkage screens, which included total 149 multiple case families. All families at least three cases diagnosed below age 60 years, one whom had been tested and found not to carry BRCA1 or BRCA2 mutation. Evidence was assessed using parametric analysis, assuming both dominant recessive mode inheritance,...
Unclassified variants (UVs, of uncertain clinical significance) are found in 13% all BRCA1/2 mutation analyses. Little is known about the counsellees' recall and interpretation a UV, its psychosocial/medical impact.Retrospective semi-structured interviews with open questions five-point Likert scales were carried out 24 counsellees who received UV result 3 years before (sd=1.9).Sixty-seven percent (16/24) recalled as non-informative DNA result; 29% pathogenic result. However, 79% interpreted...
Background Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling individuals carrying these variants. We previously showed that variant c.5096G>A p.Arg1699Gln transcriptional transactivation domain demonstrated equivocal results from a series functional assays, proposed this may confer low to moderate risk cancer. Methods Measures (report family history, segregation) were assessed...
A large number of sequence variants identified in BRCA1 and BRCA2 cannot be distinguished as either disease-causing mutations or neutral variants. These so-called unclassified (UVs) include that are located the intronic sequences BRCA2. The purpose this study was to assess use splice-site prediction programs (SSPPs) select likely affect RNA splicing. We performed vitro molecular characterization six In four cases (BRCA1, c.81–6T>A c.4986+5G>T; BRCA2, c.7617+2T>G c.8754+5G>A) a deleterious...
The identification of the two most prevalent susceptibility genes in breast cancer, BRCA1 and BRCA2, was beginning a sustained effort to uncover new explaining missing heritability this disease. Today, additional high, moderate low penetrance have been identified such as P53, PTEN, STK11, PALB2 or ATM, globally accounting for around 35 percent familial cases. In present study we used massively parallel sequencing analyze 7 BRCA1/BRCA2 negative families, each having at least 6 affected women...
Study Type – Diagnostic (validating cohort) Level of Evidence 1b What’s known on the subject? and What does study add? Scientists have found a number genetic factors that increase prostate cancer risk, including heritable mutations in genes BRCA1 BRCA2 . These are not common but can major impact, as mutation increases risk by up to seven‐fold while is thought double men under 65. The IMPACT aims determine whether targeted screening with or would lead earlier diagnosis cancers. This data from...
Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial remain unexplained. To determine whether some missing heritability is due to rare variants conferring high moderate risk, we tested for an association between c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 FANCM gene and cancer. An analysis genotyping data from 8635 cases 6625 controls different countries yielded [odds ratio (OR) = 3.93 (95%...