The role of genetic breast cancer susceptibility variants as prognostic factors

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, Aittomaki, Kristiina, Blomqvist, Carl, Shah, Mitul, Nordestgaard, Borge 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 L., Ozcelik, Hilmi, Mulligan, Anna-Marie, Glendon, Gord, Hall, Per, Czene, Kamila, Liu, Jianjun, Chang-Claude, Jenny, Wang-Gohrke, Shan, Eilber, Ursula, Nickels, Stefan, Doerk, 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., Olson, Janet E., Kosei, Matthew, Cross, Simon S., Balasubramanian, Sabapathy P., Reed, Malcolm W. R., Miron, Alexander, John, Esther M., Winqvist, Robert, Pylkas, Katri, Jukkola-Vuorinen, Arja, Kauppila, Saila, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Chenevix-Trench, Georgia, Lambrechts, Diether, Dieudonne, Anne-Sophie, Hatse, Sigrid, van Limbergen, Erik, Benitez, Javier, Milne, Roger L., Pilar Zamora, M., Arias Perez, Jose 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. and Schmidt, Marjanka K. (2012) The role of genetic breast cancer susceptibility variants as prognostic factors. Human Molecular Genetics, 21 17: 3926-3939. doi:10.1093/hmg/dds159

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Author 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
Aittomaki, Kristiina
Blomqvist, Carl
Shah, Mitul
Nordestgaard, Borge 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 L.
Ozcelik, Hilmi
Mulligan, Anna-Marie
Glendon, Gord
Hall, Per
Czene, Kamila
Liu, Jianjun
Chang-Claude, Jenny
Wang-Gohrke, Shan
Eilber, Ursula
Nickels, Stefan
Doerk, 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.
Olson, Janet E.
Kosei, Matthew
Cross, Simon S.
Balasubramanian, Sabapathy P.
Reed, Malcolm W. R.
Miron, Alexander
John, Esther M.
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sohn, Christof
Chenevix-Trench, Georgia
Lambrechts, Diether
Dieudonne, Anne-Sophie
Hatse, Sigrid
van Limbergen, Erik
Benitez, Javier
Milne, Roger L.
Pilar Zamora, M.
Arias Perez, Jose 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.
Title The role of genetic breast cancer susceptibility variants as prognostic factors
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2012-09
Sub-type Article (original research)
DOI 10.1093/hmg/dds159
Open Access Status
Volume 21
Issue 17
Start page 3926
End page 3939
Total pages 14
Place of publication Oxford, England, U.K.
Publisher Oxford University Press
Collection year 2013
Language eng
Abstract Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed 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 the 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 the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 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. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility.
Keyword Genome-Wide Association
Single-Nucleotide Polymorphisms
Confer Susceptibility
Common Variants
Atm Gene
Risk
Survival
Locus
Consortium
Women
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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Created: Tue, 25 Sep 2012, 11:14:21 EST by Matthew Lamb on behalf of School of Medicine