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Title: Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)
Authors: Hein, Rebecca ×
Maranian, Melanie
Hopper, John L
Kapuscinski, Miroslaw K
Southey, Melissa C
Park, Daniel J
Schmidt, Marjanka K
Broeks, Annegien
Hogervorst, Frans B L
Bueno-de-Mesquit, H Bas
Muir, Kenneth R
Fredericksen, Zachary
Giles, Graham G
Baglietto, Laura
McLean, Catriona A
Severi, Gianluca
Offit, Kenneth
Robson, Mark
Gaudet, Mia M
Vijai, Joseph
Alnæs, Grethe Grenaker
Lophatananon, Artitaya
Kristensen, Vessela
Børresen-Dale, Anne-Lise
John, Esther M
Miron, Alexander
Winqvist, Robert
Pylkäs, Katri
Jukkola-Vuorinen, Arja
Grip, Mervi
Andrulis, Irene L
Knight, Julia A
Rattanamongkongul, Suthee
Glendon, Gord
Mulligan, Anna Marie
Figueroa, Jonine D
García-Closas, Montserrat
Lissowska, Jolanta
Sherman, Mark E
Hooning, Maartje
Martens, John W M
Seynaeve, Caroline
Collée, Margriet
Puttawibul, Puttisak
Hall, Per
Humpreys, Keith
Czene, Kamila
Liu, Jianjun
Cox, Angela
Brock, Ian W
Cross, Simon S
Reed, Malcolm W R
Ahmed, Shahana
Ghoussaini, Maya
Fasching, Peter A
Pharoah, Paul Dp
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Jakubowska, Anna
Jaworska, Katarzyna
Durda, Katarzyna
Złowocka, Elżbieta
Sangrajrang, Suleeporn
Gaborieau, Valerie
Hein, Alexander
Brennan, Paul
McKay, James
Shen, Chen-Yang
Yu, Jyh-Cherng
Hsu, Huan-Ming
Hou, Ming-Feng
Orr, Nick
Schoemaker, Minouk
Ashworth, Alan
Swerdlow, Anthony
Ekici, Arif B
Trentham-Dietz, Amy
Newcomb, Polly A
Titus, Linda
Egan, Kathleen M
Chenevix-Trench, Georgia
Antoniou, Antonis C
Humphreys, Manjeet K
Morrison, Jonathan
Chang-Claude, Jenny
Easton, Douglas F
Beckmann, Matthias W
Dunning, Alison M
Fletcher, Olivia
Johnson, Nichola
Dos Santos Silva, Isabel
Peto, Julian
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael
Miller, Nicola
Marmee, Frederick
Schneeweiss, Andreas
Sohn, Christof
Burwinkel, Barbara
Guénel, Pascal
Cordina-Duverger, Emilie
Menegaux, Florence
Truong, Thérèse
Bojesen, Stig E
Nordestgaard, Børge G
Flyger, Henrik
Milne, Roger L
Perez, Jose Ignacio Arias
Zamora, M Pilar
Benítez, Javier
Anton-Culver, Hoda
Ziogas, Argyrios
Bernstein, Leslie
Clarke, Christina A
Brenner, Hermann
Müller, Heiko
Arndt, Volker
Stegmaier, Christa
Rahman, Nazneen
Seal, Sheila
Turnbull, Clare
Renwick, Anthony
Meindl, Alfons
Schott, Sarah
Bartram, Claus R
Schmutzler, Rita K
Brauch, Hiltrud
Hamann, Ute
Ko, Yon-Dschun
The GENICA Network
Wang-Gohrke, Shan
Dörk, Thilo
Schürmann, Peter
Karstens, Johann H
Hillemanns, Peter
Nevanlinna, Heli
Heikkinen, Tuomas
Aittomäki, Kristiina
Blomqvist, Carl
Bogdanova, Natalia V
Zalutsky, Iosif V
Antonenkova, Natalia N
Bermisheva, Marina
Prokovieva, Darya
Farahtdinova, Albina
Khusnutdinova, Elza
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana
Chen, Xiaoqing
Beesley, Jonathan
Investigators, Kconfab
AOCS Group
Lambrechts, Diether
Zhao, Hui
Neven, Patrick
Wildiers, Hans
Nickels, Stefan
Flesch-Janys, Dieter
Radice, Paolo
Peterlongo, Paolo
Manoukian, Siranoush
Barile, Monica
Couch, Fergus J
Olson, Janet E
Wang, Xianshu #
Issue Date: 2012
Publisher: Public Library of Sciene
Series Title: PLoS One vol:7 issue:8
Article number: e42380
Abstract: The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10(-7), p(heterogeneity) = 5.1×10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.
URI: 
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
Gynaecological Oncology
Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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