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

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Breast Cancer Association Consortium (Including: Muir, Kenneth (Kenneth R.) and Lophatananon, Artitaya). (2012) Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association Consortium (BCAC). PLoS ONE, Vol.7 (No.8). e42380. doi:10.1371/journal.pone.0042380 ISSN 1932-6203.

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Official URL: http://dx.doi.org/10.1371/journal.pone.0042380

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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.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Breast -- Cancer -- Genetic aspects
Journal or Publication Title: PLoS ONE
Publisher: PLOS
ISSN: 1932-6203
Official Date: 2012
Dates:
DateEvent
2012Published
Volume: Vol.7
Number: No.8
Page Range: e42380
DOI: 10.1371/journal.pone.0042380
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 22 December 2015
Date of first compliant Open Access: 22 December 2015
Funder: Seventh Framework Programme (European Commission) (FP7), Cancer Research UK (CRUK), European Union (EU), Joseph Mitchell Trust, National Institutes of Health (U.S.) (NIH), Cancer Care Ontario, Northern California Cancer Program, University of Melbourne, National Health and Medical Research Council (Australia) (NHMRC), New South Wales State Cancer Council, Victorian Health Promotion Foundation (VHPF), Victorian Breast Cancer Research Consortium, KWF Kankerbestrijding [Dutch Cancer Society], Netherlands Genomics Initiative, Breast Cancer Research Trust (Great Britain), University Hospital of Erlangen, Breakthrough Breast Cancer, Great Britain. National Health Service (NHS), Guy's & St. Thomas' NHS Foundation Trust, Oxford Biomedical Research Centre, Fondation de France, Institut National Du Cancer (France), Anses, Ligue nationale contre le cancer (France) (LNCC), France. Agence nationale de la recherche (ANR), Chief Physician Johan Boserup and Lise Boserup's Fund, Statens lægevidenskabelige forskningsråd (Denmark), Amtssygehuset i Herlev, Genoma España, Red Temática de Investigación Cooperativa en Cáncer, Asociación Española contra el Cáncer, Fondo de Investigaciones Sanitarias (Spain), Lon V Smith Foundation, California Breast Cancer Research Program, Baden-Württemberg (Germany). Ministerium für Wissenschaft, Forschung und Kunst, Deutsche Krebshilfe [German Cancer Aid], United States. Dept. of Defense (DoD), Institute of Cancer Research: Royal Cancer Hospital, Medical Research Council (Great Britain) (MRC), Great Britain. National Health Service (NHS), Universität zu Köln. Zentrum der Molekularen Medizin, Hermann von Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF), Dietmar Hopp Stiftung, Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Universität Tübingen, Evangelische Kliniken Bonn gGmbH - Waldkrankenhaus, Universität Bonn. Institut der Pathologie, Deutsches Krebsforschungszentrum Heidelberg, Deutsche Gesetzliche Unfallversicherung, Universität Ulm, Universität Hannover, Deutsche Forschungsgemeinschaft (DFG), Suomen Akatemia [Academy of Finland], Suomen Syöpäyhdistys [Cancer Society of Finland], Sigrid Jusélius stiftelse, Germany. Bundesministerium für Bildung und Forschung (BMBF), Riksföreningen mot cancer [Swedish Cancer Society], Cancer Society in Stockholm, Savon Syöpärahasto, Itä-Suomen yliopisto [University of Eastern Finland], National Breast Cancer Foundation, Queensland Cancer Fund, Cancer Council South Australia, Cancer Council Victoria, Cancer Council Tasmania, Cancer Foundation of Western Australia, United States. Army Medical Research and Materiel Command, Stichting tegen Kanker (Belgium), Hamburg Cancer Society, Germany. Bundesministerium für Bildung und Forschung (BMBF), Italy. Ministero della salute, Italy. Ministero dell'università e della ricerca scientifica e tecnologica, Fondazione Italiana per la Ricerca sul Cancro (FIRC), Associazione italiana per la ricerca sul cancro (AIRC), Breast Cancer Research Foundation, Sharon Levine Corzine Fund, Niehaus Cancer Research Initiative, Andrew Sabin Family Fund, Charles Krasne Research Fund, Norman and Carol Stone Research Initiative, Norges forskningsråd [Norwegian Research Council], Swiss Bridge Foundation, Oulun yliopisto [University of Oulu], Oulun yliopistollinen sairaala (OYS), United States. Dept. of Health and Human Services. National Cancer Institute, Märit and Hans Rausing Initiative Against Breast Cancer, Singapore. Agency for Science, Technology and Research (ASTAR), Susan G. Komen Breast Cancer Foundation, Yorkshire Cancer Research, Breast Cancer Campaign, Korea (South). Pogŏn Pokchibu, Poland. Ministerstwo Nauki i Szkolnictwa Wyższego [Ministry of Science and Higher Education] (MNiSW), Foundation for Polish Science [Fundacja na rzecz Nauki Polskiej] (FNP), National Cancer Institute (Thailand), Zhong yang yan jiu yuan [Academia Sinica (Taipei, Taiwan)], Massachusetts, Wisconsin, New Hampshire

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