DOI: 10.1093/hmg/dds159

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The role of genetic breast cancer susceptibility variants as prognostic factors

Peter A. Fasching,Paul D.P. Pharoah,Angela Cox,Heli Nevanlinna,Stig E. Bojesen,Thomas Karn,Annegien Broeks,Flora E. van Leeuwen,Laura J. Van’t Veer,Renate Udo,Alison M. Dunning,Dario Greco,Kristiina Aittomäki,Carl Blomqvist,Mitul Shah,Børge G. Nordestgaard,Henrik Flyger,John L. Hopper,Melissa C. Southey,Carmel Apicella,Montserrat García-Closas,Mark E. Sherman,Jolanta Lissowska,Caroline Seynaeve,Petra E A Huijts,Rob A.E.M. Tollenaar,Argyrios Ziogas,Arif B. Ekici,Claudia Rauh,Arto Mannermaa,Vesa Kataja,Veli Matti Kosma,Jaana M. Hartikainen,Irene L. Andrulis,Hilmi Özçelik,Anna Marie Mulligan,Gord Glendon,Per Hall,Kamila Czene,Jianjun Li,Jenny Chang‐Claude,Shan Wang-Gohrke,Ursula Eilber,Stefan Nickels,Thilo Dörk,Maria Schiekel,Michael Bremer,Tjoung Won Park-Simon,Graham G. Giles,Gianluca Severi,Laura Baglietto,Maartje J. Hooning,John W.M. Martens,Agnes Jager,Mieke Kriege,Annika Lindblom,Sara Margolin,Fergus J. Couch,Kristen N. Stevens,Janet E. Olson,Matthew L. Kosel,Simon S. Cross,Sabapathy P Balasubramanian,Malcolm W.R. Reed,Alexander Miron,Esther M. John,Robert Winqvist,Katri Pylkäs,Arja Jukkola-Vuorinen,Saila Kauppila,Barbara Burwinkel,Frederik Marmé,Andreas Schneeweiß,Christof Sohn,Georgia Chenevix-Trench,Diether Lambrechts,Anne Sophie Dieudonné,Sigrid Hatse,Erik Limbergen,Javier Benı́tez,Roger L. Milne,M. Pilar Zamora,Jose Ignacio Arias Pérez,Bernardo Bonanni,Bernard Peissel,Loris Bernard,Paolo Peterlongo,Preetha Rajaraman,Sara J. Schonfeld,Hoda Anton‐Culver,Peter Devilee,Matthias W. Beckmann,Dennis J. Slamon,Kelly‐Anne Phillips,Jonine D. Figueroa,Manjeet K. Humphreys,Douglas F. Easton,Marjanka K. Schmidt

Biology

Breast cancer

Genetics

2012

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.

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“The role of genetic breast cancer susceptibility variants as prognostic factors” is a paper by Peter A. Fasching Paul D.P. Pharoah Angela Cox Heli Nevanlinna Stig E. Bojesen Thomas Karn Annegien Broeks Flora E. van Leeuwen Laura J. Van’t Veer Renate Udo Alison M. Dunning Dario Greco Kristiina Aittomäki Carl Blomqvist Mitul Shah Børge G. Nordestgaard Henrik Flyger John L. Hopper Melissa C. Southey Carmel Apicella Montserrat García-Closas Mark E. Sherman Jolanta Lissowska Caroline Seynaeve Petra E A Huijts Rob A.E.M. Tollenaar Argyrios Ziogas Arif B. Ekici Claudia Rauh Arto Mannermaa Vesa Kataja Veli Matti Kosma Jaana M. Hartikainen Irene L. Andrulis Hilmi Özçelik Anna Marie Mulligan Gord Glendon Per Hall Kamila Czene Jianjun Li Jenny Chang‐Claude Shan Wang-Gohrke Ursula Eilber Stefan Nickels Thilo Dörk Maria Schiekel Michael Bremer Tjoung Won Park-Simon Graham G. Giles Gianluca Severi Laura Baglietto Maartje J. Hooning John W.M. Martens Agnes Jager Mieke Kriege Annika Lindblom Sara Margolin Fergus J. Couch Kristen N. Stevens Janet E. Olson Matthew L. Kosel Simon S. Cross Sabapathy P Balasubramanian Malcolm W.R. Reed Alexander Miron Esther M. John Robert Winqvist Katri Pylkäs Arja Jukkola-Vuorinen Saila Kauppila Barbara Burwinkel Frederik Marmé Andreas Schneeweiß Christof Sohn Georgia Chenevix-Trench Diether Lambrechts Anne Sophie Dieudonné Sigrid Hatse Erik Limbergen Javier Benı́tez Roger L. Milne M. Pilar Zamora Jose Ignacio Arias Pérez Bernardo Bonanni Bernard Peissel Loris Bernard Paolo Peterlongo Preetha Rajaraman Sara J. Schonfeld Hoda Anton‐Culver Peter Devilee Matthias W. Beckmann Dennis J. Slamon Kelly‐Anne Phillips Jonine D. Figueroa Manjeet K. Humphreys Douglas F. Easton Marjanka K. Schmidt published in 2012. It has an Open Access status of “bronze”. You can read and download a PDF Full Text of this paper here.