Aðalgeir Arason
A5049579554- BRCA gene mutations in cancer
- Genomic variations and chromosomal abnormalities
- Nutrition, Genetics, and Disease
- Genetic Associations and Epidemiology
- Cancer Genomics and Diagnostics
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- Breast Cancer Treatment Studies
- RNA modifications and cancer
- Ocular Oncology and Treatments
- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- PARP inhibition in cancer therapy
- MicroRNA in disease regulation
- Bioinformatics and Genomic Networks
- Male Breast Health Studies
- Nonmelanoma Skin Cancer Studies
- Microtubule and mitosis dynamics
- HER2/EGFR in Cancer Research
- Genetic Syndromes and Imprinting
National University Hospital of Iceland
2013-2024
University of Iceland
2013-2024
Reykjavík University
2010-2023
Wellcome Sanger Institute
2017
Cancer Genetics (United States)
2000-2012
American Cancer Society
2012
Mayo Clinic in Florida
2012
University of Southern California
2012
Lund University
2010-2012
Mount Sinai Hospital
2012
SummaryThe contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage mutation analysis in 237 families, each with at least four cases cancer, collected the Breast Cancer Linkage Consortium. Families were included without regard occurrence ovarian or other cancers. Overall, disease linked an estimated 52% 32% neither gene 16% (95% confidence interval [CI] 6%–28%), suggesting predisposition genes. The majority (81%) breast-ovarian families due BRCA1, most others (14%)...
Abstract Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets mutation carriers should allow further tumor characterization. Methods: We used data from 4,325 2,568 to analyze the pathology invasive breast, ovarian, contralateral cancers. Results: There was strong evidence proportion estrogen receptor (ER)-negative decreased with age at diagnosis among (P-trend = 1.2 × 10−5), but increased BRCA2, 6.8 10−6)....
The prevalence and spectrum of germline mutations in BRCA1 BRCA2 have been reported single populations, with the majority reports focused on White Europe North America. Consortium Investigators Modifiers BRCA1/2 (CIMBA) has assembled data 18,435 families 11,351 ascertained from 69 centers 49 countries six continents. This study comprehensively describes characteristics 1,650 unique 1,731 deleterious (disease-associated) identified CIMBA database. We observed substantial variation mutation...
Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used dissect this complexity stratify tumors into intrinsic gene-expression subtypes, associated distinct biology, patient outcome, genomic alterations. Additionally, breast occurring in individuals germline BRCA1 or BRCA2 mutations typically fall subtypes. We applied global DNA copy number 359 tumors. All were classified according subtypes included cases...
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...
PURPOSE Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) variable prognosis and response to therapy. We aimed investigate the heterogeneous biologic appearance clinical behavior HER2-positive tumors using molecular profiling. PATIENTS AND METHODS Hierarchical clustering expression data from 58 HER2-amplified various stage, histologic grade, estrogen (ER)...
HER2 gene amplification and protein overexpression (HER2+) define a clinically challenging subgroup of breast cancer with variable prognosis response to therapy. Although expression profiling has identified an ERBB2 molecular subtype cancer, it is clear that HER2+ tumors reside in all subtypes represent genomically biologically heterogeneous group, needed be further characterized large sample sets. Genome-wide DNA copy number profiling, using bacterial artificial chromosome (BAC) array...
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...
Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify modifying loci carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using ranked P-values associations with imputed genotype 1.4 M SNPs, 19,029 SNPs were selected and designed inclusion on custom Illumina array that included...
BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity data exists on the pathology cancers (BCs) in men BRCA1/2 mutations. Using largest available dataset, we determined whether MBCs arising mutation carriers display specific pathologic features and these differ from those female BCs (FBCs). We characterised 419 using logistic regression analysis, contrasted 9675 FBCs population-based 6351 Surveillance, Epidemiology,...
A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for cancer using mathematical models early somatic genetic deletions tumor tissues followed targeted linkage analysis. Comparative genomic hybridization was used study 61 tumors from 37 families with no identified mutations. Branching and phylogenetic tree predicted that loss 13q one earliest events hereditary cancers. In...
Abstract Loss of heterozygosity (LOH) was evaluated in 174 breast and ovarian tumors derived from 94 families with at least 3 first‐degree relatives affected either these cancers. By linkage analysis 26 were identified as having a high posterior probability being due to BRCAI (the breadovarian cancer susceptibility locus on 17q 12–21) lod scores varying 0.5 1 9.49. Tumor genotypes determined 2 constitutionally heterozygous markers flanking BRCA I total 58 families. These 52 patients, the...
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...
Breast cancer is the most often diagnosed in women. MicroRNAs (MIRs) are short RNA molecules that bind mRNA resulting their downregulation. MIR21 has been shown to be an oncomiR types, including breast cancer. Most of effects miR-21 have attributed hsa-miR-21-5p transcribed from leading strand MIR21, but hsa-miR-21-3p (miR-21-3p), lagging strand, much less studied. The aim study analyze whether expression miR-21-3p prognostic for MiR-21-3p association with survival, clinical and pathological...
<b>Objective:</b> To estimate the risk of malignant diseases in families probands with same mutation <i>BRCA2 gene</i>. <b>Design:</b> A cohort study using record linkage a breast cancer family resource and Icelandic Cancer Registry. <b>Setting:</b> Iceland. <b>Subjects:</b> Families 995 patients, from which 887 were tested for single founder 999del5 mutation; 90 had 797 did not. <b>Results:</b> Relatives significantly increased relative (RR) cancer. For first degree relatives, RR was 7.55...
The impact of an inherited BRCA2 mutation on the prognosis women with breast cancer has not been well documented. We studied effects oestrogen receptor (ER) status, other prognostic factors and treatments survival in a large cohort carriers. identified 285 patients 999del5 matched them 570 non-carrier patients. Clinical information was abstracted from patient charts pathology records supplemented by evaluation tumour grade ER status using archived tissue specimens. Univariate multivariate...
Recent population-based female breast cancer and prostate polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with risks for male BRCA1 BRCA2 pathogenic variant carriers.