DOI: 10.6084/m9.figshare.12613043
title: Metadata supporting Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

description: This metadata record describes the data generated and analysed in the study "Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer".<br>The study investigates genetic survival associations in pathogenic variant carriers from Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), genotyped on the OncoArray.<br><br><b>Data availability and sources</b>A subset of the genotype data that support the findings of this study is publicly available via dbGaP https://identifiers.org/dbgap:phs001321.v1.p1<br>CIMBA 1000 Genomes-imputed genotype data is protected in accordance with the informed consent received from the study participants and therefore cannot be made publicly available. Requests for data can be made to the CIMBA Data Access Coordination Committee. DACC approval is required to access data from the BCFR-ON, EMBRACE, GC-HBOC, HEBCS, HEBON, IHCC, IPOBCS, MCGILL, and OUH studies Phenotype data is stored in a relational database and an output would be a text file. Imputed genotype data can be requested in the QCTOOL <i>dosage</i> format (https://www.well.ox.ac.uk/~gav/qctool_v2/documentation/genotype_file_formats.html), which has been used in these analyses<br><br>The contact for data access requests is Lesley McGuffog (ljm26@medschl.cam.ac.uk), Data Manager, Department of Public Health and Primary Care, University of Cambridge<br><br>Newly discovered survival SNPs were characterized <i>in silico</i> utilizing data from the 1000 genomes and Encode projects as integrated in databases LDlink, RegulomeDB and GeneCards.<br>Candidate genes’ mRNA expression and patient survival was tested in the METABRIC data in European Genome-phenome Archive: EGAD00010000434 (1,302 breast cancer patients).<br>BCAC survival summary results are available from the University of Cambridge BCAC site<br>All summary results will be made available on the CIMBA website upon publication of the related article: http://cimba.ccge.medschl.cam.ac.uk<br>The data that support each table and figure in the related article are summarised in the excel file in this data record.<b><br></b><b>Background</b>This study investigates the survival of women carrying germline pathogenic BRCA1 or BRCA2 variants. These are the two most important genes linked to breast cancer susceptibility. The great variation in survival rates between tumors with similar characteristics and stage suggests a heritable component, e.g. genetic differences in metastatic potential sensitivity to adjuvant therapy or host factors, like tumor microenvironment interaction, immune surveillance, and efficiency in drug metabolism. Both candidate gene and genome-wide approaches have been employed to find genetic determinants patient prognosis and treatment outcome prediction.<br><br>Participants women of European ancestry diagnosed with invasive breast cancer before the age of 70 years, enrolled in studies participating in CIMBA. CIMBA studies included in analysis if sufficient follow-up data are available, at least 15 study subjects at risk during the time when five events occurred. Patients were followed from the diagnosis of the first primary breast cancer until death of any causeand censored after 15 years or when lost from follow-up<br>Supplementary table 1 of the related article lists all CIMBA studies, characteristics, sample and cohort sizes. <br>Overall sample sizes: 21 studies for carrier of BRCA1 variants (<i>n</i> = 3,008) 15 studies for carriers of BRCA2 variants (<i>n</i> = 2,009).<br><br>