Title: The role of genetic breast cancer susceptibility variants as prognostic factors
Authors: Fasching, Peter A ×
Pharoah, Paul D P
Cox, Angela
Nevanlinna, Heli
Bojesen, Stig E
Karn, Thomas
Broeks, Annegien
van Leeuwen, Flora E
van 't Veer, Laura J
Udo, Renate
Dunning, Alison M
Greco, Dario
Aittomäki, Kristiina
Blomqvist, Carl
Shah, Mitul
Nordestgaard, Børge G
Flyger, Henrik
Hopper, John L
Southey, Melissa C
Apicella, Carmel
Garcia-Closas, Montserrat
Sherman, Mark
Lissowska, Jolanta
Seynaeve, Caroline
Huijts, Petra E A
Tollenaar, Rob A E M
Ziogas, Argyrios
Ekici, Arif B
Rauh, Claudia
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M
Andrulis, Irene
Ozcelik, Hilmi
Mulligan, Anna-Marie
Glendon, Gord
Hall, Per
Czene, Kamila
Liu, Jianjun
Chang-Claude, Jenny
Wang-Gohrke, Shan
Eilber, Ursula
Nickels, Stefan
Dörk, Thilo
Schiekel, Maria
Bremer, Michael
Park-Simon, Tjoung-Won
Giles, Graham G
Severi, Gianluca
Baglietto, Laura
Hooning, Maartje J
Martens, John W M
Jager, Agnes
Kriege, Mieke
Lindblom, Annika
Margolin, Sara
Couch, Fergus J
Stevens, Kristen N
Olsen, Janet E
Kosel, Matthew
Cross, Simon S
Balasubramanian, Sabapathy P
Reed, Malcolm W R
Miron, Alexander
John, Esther
Winqvist, Robert
Pylkäs, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sohn, Christof
Chenevix-Trench, Georgia
kConFab Investigators
Lambrechts, Diether
Dieudonné, Anne-Sophie
Hatse, Sigrid
Van Limbergen, Erik
Benitez, Javier
Milne, Roger L
Zamora, Maria P
Arias Pérez, José Ignacio
Bonanni, Bernardo
Peissel, Bernard
Loris, Bernard
Peterlongo, Paolo
Rajaraman, Preetha
Schonfeld, Sara J
Anton-Culver, Hoda
Devilee, Peter
Beckmann, Matthias W
Slamon, Dennis J
Phillips, Kelly-Anne
Figueroa, Jonine D
Humphreys, Manjeet K
Easton, Douglas F
Schmidt, Marjanka K #
Issue Date: Apr-2012
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:21 issue:17 pages:3926-3939
Abstract: BACKGROUNDRecent genome-wide association studies identified eleven single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance.METHODSConfirmed BC risk SNPs rs17468277(CASP8), rs1982073(TGFB1), rs2981582(FGFR2), rs13281615(8q24), rs3817198(LSP1), rs889312(MAP3K1), rs3803662(TOX3), rs13387042(2q35), rs4973768(SLC4A7), rs6504950(COX11) and rs10941679(5p12) were genotyped for 25,853 BC patients with available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and prognosis in a different patient group.RESULTSOne of the eleven SNPs, rs3803662(TOX3) and none of 62 candidate/GWAS SNPs were associated with OS and/or BCS at P<0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action (hazard ratio (HR) of rare homozygous carriers=1.21; 95%CI: 1.09-1.35, P=0.0002 and HR=1.29; 95%CI: 1.12-1.47, P=0.0003 for OS and BCS, respectively). This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis.CONCLUSIONWith the exception of rs3803662(TOX3), there was no evidence that any of the SNPs associated with breast cancer susceptibility were associated with BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
Laboratory of Experimental Oncology
Laboratory of Experimental Radiotherapy
Gynaecological Oncology
× corresponding author
# (joint) last author

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