{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dennis J"],"funding":["Intramural NIH HHS","Cancer Research UK","World Health Organization","European Research Council","NCCDPHP CDC HHS","NIEHS NIH HHS","Medical Research Council","National Institute for Health Research (NIHR)","NCI NIH HHS","Cancer Foundation Finland sr"],"pagination":["65"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8766486"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(1)"],"pubmed_abstract":["Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance."],"journal":["Communications biology"],"pubmed_title":["Rare germline copy number variants (CNVs) and breast cancer risk."],"pmcid":["PMC8766486"],"funding_grant_id":["C5047/A10692","1000143","U19 CA148537","P01 CA087969","U01 CA176726","C12292/A11174","C1287/A10118","R01 CA128931","C1281/A12014","C1287/A10710","U01 CA179715","R01 CA128978","U01 CA098758","R01 CA132839","NU58DP006344","U19 CA148065","210067","R35 CA253187","14136","U54 CA156733","R37 CA054281","HHSN261201800009C","R01 CA177150","G1000143","Z01 ES049030","C8221/A19170","16563","Z01 ES049033","HHSN261201800009I","C490/A16561","P30 CA033572","NF-SI-0512-10114","P30 ES010126","R01 CA176785","P50 CA116201","U01 CA058860","U01 CA199277","001","R01 CA063464","P50 CA058223","R01 CA054281","P30 CA068485","P30 CA015083","MR/M012190/1","Z01 CP010119","190149","K07 CA092044","C570/A16491","UM1 CA164973","UM1 CA186107","PPRPGM-Nov20\\100002","C1287/A16563","HHSN261201800032C","R01 CA047147","C8197/A16565","HHSN261201800032I","200132","R01 CA116167","R01 CA047305","UM1 CA164920","P30 CA023100","U01 CA063464","U01 CA164920","R01 CA077398","UM1 CA164917","U01 CA164973","R01 CA097396","HHSN261201800015C","C490/A10124","R01 CA069664","MR/N003284/1","294576","R01 CA100374","HHSN261201800015I","R01 CA192393","C5047/A8384","UM1 CA176726","R01 CA140286","G0401527","R01 CA058860","U19 CA148112","C5047/A15007","Z01 ES044005"],"pubmed_authors":["Mavroudis D","Taylor JA","Flyger H","Dork T","Southey MC","Cross SS","Fritschi L","Clarke CL","NBCS Collaborators","Perou CM","Ahearn TU","Spurdle A","Koutros S","Terry MB","kConFab/AOCS Investigators","Dorling L","Easton DF","Hoppe R","Muranen TA","Baxter R","Wolk A","Teras LR","Fletcher O","Sahlberg KK","Jones ME","Kitahara CM","Wendt C","Zheng W","Fox S","Hall P","Schmutzler RK","Marsh D","Figueroa J","Brenner H","Truong T","Winqvist R","Lacey JV","Kaaks R","Tyrer JP","Murphy RA","Benitez J","Bojesen SE","Plaseska-Karanfilska D","Bogdanova NV","Yang XR","Thorne H","Kirk J","Kurian AW","Ogrodniczak A","Smeets A","Behrens S","John EM","Ziogas A","Peterlongo P","Antonenkova NN","Sachchithananthan M","Cox A","Gago-Dominguez M","Jung A","Lambrechts D","Manoukian S","Rennert G","Yip D","Simpson P","Ko YD","Dossus L","Clarke C","Dunning AM","Larson NL","Kosma VM","Collee JM","Garcia-Closas M","Kubelka-Sabit K","Andrulis IL","Engebraten O","Kristensen VN","Olsson H","Guenel P","Pharoah PDP","Carpenter J","Walker LC","Jager A","Wang Q","Swerdlow AJ","Keeman R","Evans DG","Lindeman G","Couch FJ","Simard J","Davis A","Chenevix-Trench G","Gram IT","de Fazio A","Bolla MK","Milne RL","Chang-Claude J","Graham D","Aronson KJ","Freeman LEB","Hahnen E","Howell A","CTS Consortium","Fasching PA","Gabrielson M","Schmidt MK","Soucy P","Nevanlinna H","Michailidou K","Arndt V","Eriksson M","Kraft P","Khusnutdinova E","Saloustros E","Martinez E","Alnæs GIG","Anton-Culver H","Johnson N","Vachon CM","Geisler J","Pylkas K","Linet M","Milne R","ABCTB Investigators","Tomlinson I","Lacey J","Hollestelle A","Troester MA","Scott R","Beckmann MW","Devilee P","Giles GG","Tamimi RM","Haiman CA","Borresen-Dale AL","Gonzalez-Neira A","Park-Simon TW","Czene K","Margolin S","Southey M","Sandler DP","Dennis J","Sawyer EJ","Olson JE","Eliassen AH","Campbell I","Hopper JL","Shibli R","Naume B","Bermisheva M","Castelao JE","Jakubowska A","Mannermaa A","Pathmanathan N"],"additional_accession":[]},"is_claimable":false,"name":"Rare germline copy number variants (CNVs) and breast cancer risk.","description":"Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2026-05-09T03:01:04.663Z","creation":"2025-04-06T14:57:30.062Z"},"accession":"S-EPMC8766486","cross_references":{"pubmed":["35042965"],"doi":["10.1038/s42003-021-02990-6"]}}