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Title: Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium
Authors: Broeks, Annegien ×
Schmidt, Marjanka K
Sherman, Mark E
Couch, Fergus J
Hopper, John L
Dite, Gillian S
Apicella, Carmel
Smith, Letitia D
Hammet, Fleur
Southey, Melissa C
Van 't Veer, Laura J
Karstens, Johann H
Hillemanns, Peter
Dörk, Thilo
Nevanlinna, Heli A
Heikkinen, Tuomas
Heikkilä, Päivi
Blomqvist, Carl
Aittomäki, Kristiina
Aaltonen, Kirsimari
Lindblom, Annika
Tollenaar, Rob A E M
Margolin, Sara
Mannerma, Arto
Kosma, Veli-Matti
Kauppinen, Jaana M
Kataja, Vesa
Auvinen, Päivi
Eskelinen, Matti
Soini, Ylermi
Chenevix-Trench, Georgia
Spurdle, Amanda B
Van Asperen, Christi J
Beesley, Jonathan
Chen, Xiaoqing
Holland, Helene
kConFab
AOCS
Lambrechts, Diether
Claes, Bart
Vandorpe, Thijs
Neven, Patrick
Wildiers, Hans
Seynaeve, Caroline S
Flesch-Janys, Dieter
Hein, Rebecca
Löning, Thomas
Kosel, Matthew
Fredericksen, Zachary S
Wang, Xianshu
Giles, Graham G
Baglietto, Laura
Severi, Gianluca
McLean, Catriona
Chanock, Stephen J
Haiman, Christopher A
Henderson, Brian E
Le Marchand, Loic
Kolonel, Laurence N
Grenaker Alnæs, Grethe
Kristensen, Vessela
Børresen-Dale, Anne-Lise
Hunter, David J
Hankinson, Susan E
Andrulis, Irene L
Lissowska, Jolanta
Marie Mulligan, Anna
O'Malley, Frances P
Devilee, Peter
Huijts, Petra E A
Brinton, Louise
Peplonska, Beata
Figueroa, Jonine
Yang, Xiaohong R
Hooning, Maartje J
de Groot, Renate
Hollestelle, Antoinette
Oldenburg, Rogier A
Jager, Agnes
Kriege, Mieke
Ozturk, Bahar
van Leenders, Geert J L H
Hall, Per
Czene, Kamila
Humphreys, Keith
Liu, Jianjun
Smit, Vincent T H B M
Cox, Angela
Connley, Daniel
Cramp, Helen E
Cross, Simon S
Balasubramanian, Sabapathy P
Reed, Malcolm W R
Dunning, Alison M
Easton, Douglas F
Humphreys, Manjeet K
Caldas, Carlos
Fasching, Peter A
Blows, Fiona
Driver, Kristy
Provenzano, Elena
Lubinski, Jan
Jakubowska, Anna
Huzarski, Tomasz
Byrski, Tomasz
Cybulski, Cezary
Gorski, Bohdan
Gronwald, Jacek
Beckmann, Matthias W
Brennan, Paul
Sangrajrang, Suleeporn
Gaborieau, Valerie
Shen, Chen-Yang
Hsiung, Chia-Ni
Yu, Jyh-Cherng
Chen, Shou-Tung
Hsu, Giu-Cheng
Hou, Ming-Feng
Huang, Chiun-Sheng
Jud, Sebastian
Anton-Culver, Hoda
Ziogas, Argyrios
Pharoah, Paul D P
Garcia-Closas, Montserrat
Ekici, Arif B
Hartmann, Arndt
Hein, Alexander
Schulz-Wendtland, Ruediger
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sinn, Hans-Peter
Sohn, Christof
Tchatchou, Sandrine
Bojesen, Stig E
Nordestgaard, Børge G
Flyger, Henrik
Orsted, David D
Kaur-Knudsen, Diljit
Milne, Roger L
Pérez, Jose I Arias
Zamora, Pilar
Rodríguez, Primitiva Menéndez
Benítez, Javier
Brauch, Hiltrud
Justenhoven, Christina
The Genica Network
Hamann, Ute
Fischer, Hans-Peter
Brüning, Thomas
Pesch, Beate
Chang-Claude, Jenny
Wang-Gohrke, Shan
Bremer, Michael #
Issue Date: Aug-2011
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:20 issue:16 pages:3289-3303
Abstract: Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10(-18)), rs3803662 (16q12) (P = 3.7 × 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10(-6) and P = 4.1 × 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
Vesalius Research Centre (-)
Laboratory of Experimental Oncology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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