Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

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-Mesquita, H Bas

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 - Isabel, Dos Santos Silva

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 - Network, GENICA

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 - Investigators, Kconfab

AU - Group, AOCS

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 D P

AU - Kang, Daehee

AU - Yoo, Keun-Young

AU - Noh, Dong-Young

AU - Jakubowska, Anna

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Złowocka, Elżbieta

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

Y1 - 2012

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), 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.

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), 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.

KW - Humans

KW - Female

KW - Risk Factors

KW - Europe

KW - Breast Neoplasms/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Genetic Predisposition to Disease

KW - Receptors, Estrogen/genetics

KW - Genome-Wide Association Study

KW - Asia

KW - Chromosomes, Human, Pair 6/genetics

KW - Haplotypes/genetics

KW - Linkage Disequilibrium/genetics

KW - Humans

KW - Female

KW - Risk Factors

KW - Europe

KW - Breast Neoplasms/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Genetic Predisposition to Disease

KW - Receptors, Estrogen/genetics

KW - Genome-Wide Association Study

KW - Asia

KW - Chromosomes, Human, Pair 6/genetics

KW - Haplotypes/genetics

KW - Linkage Disequilibrium/genetics

U2 - 10.1371/journal.pone.0042380

DO - 10.1371/journal.pone.0042380

M3 - SCORING: Journal article

VL - 7

SP - 42380

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 8

M1 - 8

ER -