Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

Horne HN, Chung CC, Zhang H, Yu K, Prokunina-Olsson L, Michailidou K, Bolla MK, Wang Q, Dennis J, Hopper JL, Southey MC, Schmidt MK, Broeks A, Muir K, Lophatananon A, Fasching P, Beckmann M, Fletcher O, Johnson N, Sawyer EJ, Tomlinson I, Burwinkel B, Marme F, Guenel P, Truong T, Bojesen SE, Flyger H, Benitez J, Gonzalez-Neira A, Anton-Culver H, Neuhausen SL, Brenner H, Arndt V, Meindl A, Schmutzler RK, Brauch H, Hamann U, Nevanlinna H, Khan S, Matsuo K, Iwata H, Dork T, Bogdanova NV, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Chenevix-Trench G, Wu AH, Den Berg DV, Smeets A, Zhao H, Chang-Claude J, Rudolph A, Radice P, Barile M, Couch FJ, Vachon C, Giles GG, Milne RL, Haiman CA, Le Marchand L, Goldberg MS, Teo SH, Taib NAM, Kristensen V, Borresen-Dale AL, Zheng W, Shrubsole M, Winqvist R, Jukkola-Vuorinen A, Andrulis IL, Knight JA, Devilee P, Seynaeve C, Garcia-Closas M, Czene K, Darabi H, Hollestelle A, Martens JWM, Li J, Lu W, Shu XO, Cox A, Cross SS, Blot W, Cai Q, Shah M, Luccarini C, Baynes C, Harrington P, Kang D, Choi JY, Hartman M, Chia KS, Kabisch M, Torres D, Jakubowska A, Lubinski J, Sangrajrang S, Brennan P, Slager S, Yannoukakos D, Shen CY, Hou MF, Swerdlow A, Orr N, Simard J, Hall P, Pharoah PDP, Easton DF, Chanock SJ, Dunning AM, Figueroa JD (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 11

Journal Issue: 8

DOI: 10.1371/journal.pone.0160316

Abstract

The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

Authors with CRIS profile

Involved external institutions

National Cancer Institute (NCI) United States (USA) (US) University of Cambridge United Kingdom (GB) The University of Melbourne Australia (AU) Antoni van Leeuwenhoek Netherlands (NL) University of Warwick United Kingdom (GB) King’s College London United Kingdom (GB) University of Oxford United Kingdom (GB) 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) Copenhagen University Hospital Denmark (DK) University of California Irvine United States (USA) (US) Beckman Research Institute of City of Hope (BRI) United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Technische Universität München (TUM) Germany (DE) Universitätsklinikum Köln Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Karolinska Institute Sweden (SE) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) University of Southern California (USC) United States (USA) (US) Mayo Clinic United States (USA) (US) University of Malaya (UM) / Universiti Malaya Malaysia (MY) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Vanderbilt University United States (USA) (US) Oulun Yliopisto / University of Oulo Finland (FI) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) National University of Singapore (NUS) Singapore (SG) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Aichi Cancer Center Research Institute Japan (JP) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Cancer Research Initiatives Foundation (CARIF) / Cancer Research Malaysia (CRM) Malaysia (MY) University of Sheffield United Kingdom (GB) China Medical University (CMU) / 中國醫藥大學 Taiwan (TW) The Institute of Cancer Research (ICR) United Kingdom (GB) Kyushu University / 九州大学 Japan (JP) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC)) Belgium (BE) Mount Sinai Hospital (MSH) Canada (CA) Leiden University Netherlands (NL) Erasmus University Medical Center (MC) Netherlands (NL) Shanghai Center For Disease Control And Prevention (SCDC) China (CN) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Kaohsiung Medical University (KMU) / 高雄醫學大學 Taiwan (TW) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) University of Hawaii (U.H.) United States (USA) (US) McGill University Canada (CA) International Agency for Research on Cancer (IARC) France (FR) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) Université Laval (UL) Canada (CA)

How to cite

APA:

Horne, H.N., Chung, C.C., Zhang, H., Yu, K., Prokunina-Olsson, L., Michailidou, K.,... Figueroa, J.D. (2016). Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus. PLoS ONE, 11(8). https://dx.doi.org/10.1371/journal.pone.0160316

MLA:

Horne, Hisani N., et al. "Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus." PLoS ONE 11.8 (2016).

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