PLoS ONE (Jan 2012)

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

  • Rebecca Hein,
  • Melanie Maranian,
  • John L Hopper,
  • Miroslaw K Kapuscinski,
  • Melissa C Southey,
  • Daniel J Park,
  • Marjanka K Schmidt,
  • Annegien Broeks,
  • Frans B L Hogervorst,
  • H Bas Bueno-de-Mesquita,
  • Kenneth R Muir,
  • Artitaya Lophatananon,
  • Suthee Rattanamongkongul,
  • Puttisak Puttawibul,
  • Peter A Fasching,
  • Alexander Hein,
  • Arif B Ekici,
  • Matthias W Beckmann,
  • Olivia Fletcher,
  • Nichola Johnson,
  • Isabel dos Santos Silva,
  • Julian Peto,
  • Elinor Sawyer,
  • Ian Tomlinson,
  • Michael Kerin,
  • Nicola Miller,
  • Frederick Marmee,
  • Andreas Schneeweiss,
  • Christof Sohn,
  • Barbara Burwinkel,
  • Pascal Guénel,
  • Emilie Cordina-Duverger,
  • Florence Menegaux,
  • Thérèse Truong,
  • Stig E Bojesen,
  • Børge G Nordestgaard,
  • Henrik Flyger,
  • Roger L Milne,
  • Jose Ignacio Arias Perez,
  • M Pilar Zamora,
  • Javier Benítez,
  • Hoda Anton-Culver,
  • Argyrios Ziogas,
  • Leslie Bernstein,
  • Christina A Clarke,
  • Hermann Brenner,
  • Heiko Müller,
  • Volker Arndt,
  • Christa Stegmaier,
  • Nazneen Rahman,
  • Sheila Seal,
  • Clare Turnbull,
  • Anthony Renwick,
  • Alfons Meindl,
  • Sarah Schott,
  • Claus R Bartram,
  • Rita K Schmutzler,
  • Hiltrud Brauch,
  • Ute Hamann,
  • Yon-Dschun Ko,
  • GENICA Network,
  • Shan Wang-Gohrke,
  • Thilo Dörk,
  • Peter Schürmann,
  • Johann H Karstens,
  • Peter Hillemanns,
  • Heli Nevanlinna,
  • Tuomas Heikkinen,
  • Kristiina Aittomäki,
  • Carl Blomqvist,
  • Natalia V Bogdanova,
  • Iosif V Zalutsky,
  • Natalia N Antonenkova,
  • Marina Bermisheva,
  • Darya Prokovieva,
  • Albina Farahtdinova,
  • Elza Khusnutdinova,
  • Annika Lindblom,
  • Sara Margolin,
  • Arto Mannermaa,
  • Vesa Kataja,
  • Veli-Matti Kosma,
  • Jaana Hartikainen,
  • Xiaoqing Chen,
  • Jonathan Beesley,
  • Kconfab Investigators,
  • AOCS Group,
  • Diether Lambrechts,
  • Hui Zhao,
  • Patrick Neven,
  • Hans Wildiers,
  • Stefan Nickels,
  • Dieter Flesch-Janys,
  • Paolo Radice,
  • Paolo Peterlongo,
  • Siranoush Manoukian,
  • Monica Barile,
  • Fergus J Couch,
  • Janet E Olson,
  • Xianshu Wang,
  • Zachary Fredericksen,
  • Graham G Giles,
  • Laura Baglietto,
  • Catriona A McLean,
  • Gianluca Severi,
  • Kenneth Offit,
  • Mark Robson,
  • Mia M Gaudet,
  • Joseph Vijai,
  • Grethe Grenaker Alnæs,
  • Vessela Kristensen,
  • Anne-Lise Børresen-Dale,
  • Esther M John,
  • Alexander Miron,
  • Robert Winqvist,
  • Katri Pylkäs,
  • Arja Jukkola-Vuorinen,
  • Mervi Grip,
  • Irene L Andrulis,
  • Julia A Knight,
  • Gord Glendon,
  • Anna Marie Mulligan,
  • Jonine D Figueroa,
  • Montserrat García-Closas,
  • Jolanta Lissowska,
  • Mark E Sherman,
  • Maartje Hooning,
  • John W M Martens,
  • Caroline Seynaeve,
  • Margriet Collée,
  • Per Hall,
  • Keith Humpreys,
  • Kamila Czene,
  • Jianjun Liu,
  • Angela Cox,
  • Ian W Brock,
  • Simon S Cross,
  • Malcolm W R Reed,
  • Shahana Ahmed,
  • Maya Ghoussaini,
  • Paul D P Pharoah,
  • Daehee Kang,
  • Keun-Young Yoo,
  • Dong-Young Noh,
  • Anna Jakubowska,
  • Katarzyna Jaworska,
  • Katarzyna Durda,
  • Elżbieta Złowocka,
  • Suleeporn Sangrajrang,
  • Valerie Gaborieau,
  • Paul Brennan,
  • James McKay,
  • Chen-Yang Shen,
  • Jyh-Cherng Yu,
  • Huan-Ming Hsu,
  • Ming-Feng Hou,
  • Nick Orr,
  • Minouk Schoemaker,
  • Alan Ashworth,
  • Anthony Swerdlow,
  • Amy Trentham-Dietz,
  • Polly A Newcomb,
  • Linda Titus,
  • Kathleen M Egan,
  • Georgia Chenevix-Trench,
  • Antonis C Antoniou,
  • Manjeet K Humphreys,
  • Jonathan Morrison,
  • Jenny Chang-Claude,
  • Douglas F Easton,
  • Alison M Dunning

DOI
https://doi.org/10.1371/journal.pone.0042380
Journal volume & issue
Vol. 7, no. 8
p. e42380

Abstract

Read online

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.