Résumé
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, pheterogeneity = 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.
langue originale | Anglais |
---|---|
Numéro d'article | e42380 |
journal | PLoS ONE |
Volume | 7 |
Numéro de publication | 8 |
Les DOIs | |
état | Publié - 7 août 2012 |
Modification externe | Oui |
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Dans: PLoS ONE, Vol 7, Numéro 8, e42380, 07.08.2012.
Résultats de recherche: Contribution à un journal › Article › Revue par des pairs
TY - JOUR
T1 - Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)
AU - Hein, Rebecca
AU - Maranian, Melanie
AU - Hopper, John L.
AU - Kapuscinski, Miroslaw K.
AU - Southey, Melissa C.
AU - Park, Daniel J.
AU - Schmidt, Marjanka K.
AU - Broeks, Annegien
AU - Hogervorst, Frans B.L.
AU - Bueno-de-Mesquit, H. Bas
AU - Muir, Kenneth R.
AU - Lophatananon, Artitaya
AU - Rattanamongkongul, Suthee
AU - Puttawibul, Puttisak
AU - Fasching, Peter A.
AU - Hein, Alexander
AU - Ekici, Arif B.
AU - Beckmann, Matthias W.
AU - Fletcher, Olivia
AU - Johnson, Nichola
AU - dos Santos Silva, Isabel
AU - Peto, Julian
AU - Sawyer, Elinor
AU - Tomlinson, Ian
AU - Kerin, Michael
AU - Miller, Nicola
AU - Marmee, Frederick
AU - Schneeweiss, Andreas
AU - Sohn, Christof
AU - Burwinkel, Barbara
AU - Guénel, Pascal
AU - Cordina-Duverger, Emilie
AU - Menegaux, Florence
AU - Truong, Thérèse
AU - Bojesen, Stig E.
AU - Nordestgaard, Børge G.
AU - Flyger, Henrik
AU - Milne, Roger L.
AU - Perez, Jose Ignacio Arias
AU - Zamora, M. Pilar
AU - Benítez, Javier
AU - Anton-Culver, Hoda
AU - Ziogas, Argyrios
AU - Bernstein, Leslie
AU - Clarke, Christina A.
AU - Brenner, Hermann
AU - Müller, Heiko
AU - Arndt, Volker
AU - Stegmaier, Christa
AU - Rahman, Nazneen
AU - Seal, Sheila
AU - Turnbull, Clare
AU - Renwick, Anthony
AU - Meindl, Alfons
AU - Schott, Sarah
AU - Bartram, Claus R.
AU - Schmutzler, Rita K.
AU - Brauch, Hiltrud
AU - Hamann, Ute
AU - Ko, Yon Dschun
AU - Wang-Gohrke, Shan
AU - Dörk, Thilo
AU - Schürmann, Peter
AU - Karstens, Johann H.
AU - Hillemanns, Peter
AU - Nevanlinna, Heli
AU - Heikkinen, Tuomas
AU - Aittomäki, Kristiina
AU - Blomqvist, Carl
AU - Bogdanova, Natalia V.
AU - Zalutsky, Iosif V.
AU - Antonenkova, Natalia N.
AU - Bermisheva, Marina
AU - Prokovieva, Darya
AU - Farahtdinova, Albina
AU - Khusnutdinova, Elza
AU - Lindblom, Annika
AU - Margolin, Sara
AU - Mannermaa, Arto
AU - Kataja, Vesa
AU - Kosma, Veli Matti
AU - Hartikainen, Jaana
AU - Chen, Xiaoqing
AU - Beesley, Jonathan
AU - Lambrechts, Diether
AU - Zhao, Hui
AU - Neven, Patrick
AU - Wildiers, Hans
AU - Nickels, Stefan
AU - Flesch-Janys, Dieter
AU - Radice, Paolo
AU - Peterlongo, Paolo
AU - Manoukian, Siranoush
AU - Barile, Monica
AU - Couch, Fergus J.
AU - Olson, Janet E.
AU - Wang, Xianshu
AU - Fredericksen, Zachary
AU - Giles, Graham G.
AU - Baglietto, Laura
AU - McLean, Catriona A.
AU - Severi, Gianluca
AU - Offit, Kenneth
AU - Robson, Mark
AU - Gaudet, Mia M.
AU - Vijai, Joseph
AU - Alnæs, Grethe Grenaker
AU - Kristensen, Vessela
AU - Børresen-Dale, Anne Lise
AU - John, Esther M.
AU - Miron, Alexander
AU - Winqvist, Robert
AU - Pylkäs, Katri
AU - Jukkola-Vuorinen, Arja
AU - Grip, Mervi
AU - Andrulis, Irene L.
AU - Knight, Julia A.
AU - Glendon, Gord
AU - Mulligan, Anna Marie
AU - Figueroa, Jonine D.
AU - García-Closas, Montserrat
AU - Lissowska, Jolanta
AU - Sherman, Mark E.
AU - Hooning, Maartje
AU - Martens, John W.M.
AU - Seynaeve, Caroline
AU - Collée, Margriet
AU - Hall, Per
AU - Humpreys, Keith
AU - Czene, Kamila
AU - Liu, Jianjun
AU - Cox, Angela
AU - Brock, Ian W.
AU - Cross, Simon S.
AU - Reed, Malcolm W.R.
AU - Ahmed, Shahana
AU - Ghoussaini, Maya
AU - Pharoah, Paul DP
AU - Kang, Daehee
AU - Yoo, Keun Young
AU - Noh, Dong Young
AU - Jakubowska, Anna
AU - Jaworska, Katarzyna
AU - Durda, Katarzyna
AU - Złowocka, Elzbieta
AU - Sangrajrang, Suleeporn
AU - Gaborieau, Valerie
AU - Brennan, Paul
AU - McKay, James
AU - Shen, Chen Yang
AU - Yu, Jyh Cherng
AU - Hsu, Huan Ming
AU - Hou, Ming Feng
AU - Orr, Nick
AU - Schoemaker, Minouk
AU - Ashworth, Alan
AU - Swerdlow, Anthony
AU - Trentham-Dietz, Amy
AU - Newcomb, Polly A.
AU - Titus, Linda
AU - Egan, Kathleen M.
AU - Chenevix-Trench, Georgia
AU - Antoniou, Antonis C.
AU - Humphreys, Manjeet K.
AU - Morrison, Jonathan
AU - Chang-Claude, Jenny
AU - Easton, Douglas F.
AU - Dunning, Alison M.
PY - 2012/8/7
Y1 - 2012/8/7
N2 - 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, pheterogeneity = 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.
AB - 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, pheterogeneity = 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.
UR - http://www.scopus.com/inward/record.url?scp=84865061552&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0042380
DO - 10.1371/journal.pone.0042380
M3 - Article
C2 - 22879957
AN - SCOPUS:84865061552
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e42380
ER -