Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)

Hein R, Maranian M, Hopper JL, Kapuscinski MK, Southey MC, Park DJ, Schmidt MK, Broeks A, Hogervorst FBL, Bueno-De-Mesquit HB, Muir KR, Lophatananon A, Rattanamongkongul S, Puttawibul P, Fasching P, Hein A, Ekici AB, Beckmann M, Fletcher O, Johnson N, Silva IDS, Peto J, Sawyer E, Tomlinson I, Kerin M, Miller N, Marmee F, Schneeweiss A, Sohn C, Burwinkel B, Guenel P, Cordina-Duverger E, Menegaux F, Truong T, Bojesen SE, Nordestgaard BG, Flyger H, Milne RL, Arias Perez JI, Pilar Zamora M, Benitez J, Anton-Culver H, Ziogas A, Bernstein L, Clarke CA, Brenner H, Mueller H, Arndt V, Stegmaier C, Rahman N, Seal S, Turnbull C, Renwick A, Meindl A, Schott S, Bartram CR, Schmutzler RK, Brauch H, Hamann U, Ko YD, Wang-Gohrke S, Doerk T, Schuermann P, Karstens JH, Hillemanns P, Nevanlinna H, Heikkinen T, Aittomaki K, Blomqvist C, Bogdanova NV, Zalutsky IV, Antonenkova NN, Bermisheva M, Prokovieva D, Farahtdinova A, Khusnutdinova E, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen J, Chen X, Beesley J, Lambrechts D, Zhao H, Neven P, Wildiers H, Nickels S, Flesch-Janys D, Radice P, Peterlongo P, Manoukian S, Barile M, Couch FJ, Olson JE, Wang X, Fredericksen Z, Giles GG, Baglietto L, Mclean CA, Severi G, Offit K, Robson M, Gaudet MM, Vijai J, Alnaes GG, Kristensen V, Borresen-Dale AL, John EM, Miron A, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Figueroa JD, Garcia-Closas M, Lissowska J, Sherman ME, Hooning M, Martens JWM, Seynaeve C, Collee M, Hall P, Humpreys K, Czene K, Liu J, Cox A, Brock IW, Cross SS, Reed MWR, Ahmed S, Ghoussaini M, Pharoah PDP, Kang D, Yoo KY, Noh DY, Jakubowska A, Jaworska K, Durda K, Zlowocka E, Sangrajrang S, Gaborieau V, Brennan P, Mckay J, Shen CY, Yu JC, Hsu HM, Hou MF, Orr N, Schoemaker M, Ashworth A, Swerdlow A, Trentham-Dietz A, Newcomb PA, Titus L, Egan KM, Chenevix-Trench G, Antoniou AC, Humphreys MK, Morrison J, Chang-Claude J, Easton DF, Dunning AM (2012)

Publication Type: Journal article

Publication year: 2012

Journal

Book Volume: 7

Article Number: e42380

Journal Issue: 8

DOI: 10.1371/journal.pone.0042380

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, 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. © 2012 Hein et al.

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Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Cambridge United Kingdom (GB) The University of Melbourne Australia (AU) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of California Irvine United States (USA) (US) City of Hope Medical Center United States (USA) (US) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) Karolinska Institute Sweden (SE) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) University of Eastern Finland Finland (FI) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Istituto di ricovero e cura a carattere scientifico (IRCCS) Italy (IT) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Mayo Clinic United States (USA) (US) The Alfred Hospital Australia (AU) Memorial Sloan Kettering Cancer Center United States (USA) (US) American Cancer Society United States (USA) (US) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Antoni van Leeuwenhoek Netherlands (NL) Netherlands National Institute for Public Health and the Environment / Rijksinstituut voor Volksgezondheid en Milieu (RIVM) Netherlands (NL) University of Warwick United Kingdom (GB) Srinakharinwirot University / มหาวิทยาลัยศรีนครินทรวิโรฒ Thailand (TH) Prince of Songkla University, PSU Thailand (TH) The Institute of Cancer Research (ICR) United Kingdom (GB) London School of Hygiene and Tropical Medicine United Kingdom (GB) King’s College London United Kingdom (GB) University of Oxford United Kingdom (GB) University Hospital Galway Ireland (IE) Ruprecht-Karls-Universität Heidelberg Germany (DE) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) University of Copenhagen Denmark (DK) Hospital Monte Naranco Spain (ES) Hospital Universitario La Paz Spain (ES) Technische Universität München (TUM) Germany (DE) Universitätsklinikum Köln Germany (DE) Eberhard Karls Universität Tübingen Germany (DE) Evangelische Kliniken Bonn gGmbH Germany (DE) Universität Ulm Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Cancer Prevention Institute of California (CPIC) United States (USA) (US) Oulun Yliopisto / University of Oulo Finland (FI) Cancer Care Ontario Canada (CA) University of Toronto Canada (CA) National Cancer Institute (NCI) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Genome Institute of Singapore Singapore (SG) University of Sheffield United Kingdom (GB) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) International Agency for Research on Cancer (IARC) France (FR) Academia Sinica / 中央研究院 Taiwan (TW) Tri-Service General Hospital (TSGH) / 三軍總醫院 Taiwan (TW) Dana–Farber Cancer Institute United States (USA) (US) Kaohsiung Medical University (KMU) / 高雄醫學大學 Taiwan (TW) University of Wisconsin - Madison United States (USA) (US) Dartmouth-Hitchcock Medical Center (DHMC) United States (USA) (US) University of South Florida (USF) United States (USA) (US)

How to cite

APA:

Hein, R., Maranian, M., Hopper, J.L., Kapuscinski, M.K., Southey, M.C., Park, D.J.,... Dunning, A.M. (2012). Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC). PLoS ONE, 7(8). https://doi.org/10.1371/journal.pone.0042380

MLA:

Hein, Rebecca, et al. "Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)." PLoS ONE 7.8 (2012).

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