Association analysis identifies 65 new breast cancer risk loci

Dwek, M. and Presneau, Nadège 2017. Association analysis identifies 65 new breast cancer risk loci. Nature.

TitleAssociation analysis identifies 65 new breast cancer risk loci
AuthorsDwek, M. and Presneau, Nadège
Abstract

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10−8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Keywordsbreast cancer, risk, genetic, in silico, polymorphisms
JournalNature
ISSN0028-0836
Year2017
PublisherNature Publishing Group
Digital Object Identifier (DOI)doi:10.1038/nature24284
Publication dates
Published23 Oct 2017

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Swann, R., Perkins, A., Dahya, P., Woodside, J., Dutton, S., Robertson, C.E., Velentzis, L.S., Leathem, A. and Dwek, M. 2011. Abstract B76 - An overview of the DietCompLyf study - a multicentre UK study to evaluate the role of diet, lifestyle and complementary medicine use on breast cancer recurrence. National Cancer Research Institute (NCRI) Cancer Conference 2011. BT Convention Centre, Liverpool, UK 06 - 09 Nov 2011

Separation and characterization of different isoform populations of PSA in seminal fluid
Lines, A., Clarke, O., Dwek, M., Packer, S. and Edwards, R. 2011. Separation and characterization of different isoform populations of PSA in seminal fluid. American Association for Clinical Chemists Meeting. Atlanta, Georgia 15 - 19 Jul 2011

Abstract LB14 - Lectin microarray profilling of metastatic breast cancers
Fry, S., Afrough, B., Lomax-Browne, H., Timms, J.F., Velentzis, L.S. and Dwek, M. 2011. Abstract LB14 - Lectin microarray profilling of metastatic breast cancers. National Cancer Research Institute (NCRI) Cancer Conference 2011. BT Convention Centre, Liverpool, UK 06 - 09 Nov 2011

Breast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells
Ramessur, K.T., Greenwell, P., Nash, R. and Dwek, M. 2010. Breast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells. British Journal of Biomedical Science. 67 (4), pp. 189-196.

Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions
Dwek, M. 2010. Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions. Discovery-Summit. Majestic Barrière Hotel, Cannes, France 22nd – 24th March 2010

Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions
Dwek, M. 2010. Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions. Informa Life Sciences 6th Annual Next Generation Protein Therapeutics. Sheraton Brussels Hotel, Belgium 28th – 29th September 2010

GalNAc-recognition by lectins for cancer prognostication
Dwek, M. 2010. GalNAc-recognition by lectins for cancer prognostication. 105th Annual Meeting of the Anatomische Gesellschaft. Hamburg, Germany 29th March 2010

An evaluation of breast cancer cell line sialyltransferase expression levels and assessment of possible correlation with HPA lectin binding profiles
Blaszczak, E., Greenwell, G. and Dwek, M. 2010. An evaluation of breast cancer cell line sialyltransferase expression levels and assessment of possible correlation with HPA lectin binding profiles. Horizons in Molecular Biology: International PhD Student Symposium. Göttingen, Germany 27 - 30 Sep 2010

A sensitive assay to measure biomarker glycosylation demonstrates increased fucosylation of prostate specific antigen (PSA) in patients with prostate cancer compared with benign prostatic hyperplasia
Dwek, M., Jenks, A. and Leathem, A. 2010. A sensitive assay to measure biomarker glycosylation demonstrates increased fucosylation of prostate specific antigen (PSA) in patients with prostate cancer compared with benign prostatic hyperplasia. Clinica Chimica Acta. 411 (23-24), pp. 1935-1939.

Cancer prognostication using a recombinant form of the lectin from Helix pomatia agglutinin
Dwek, M., Markiv, A. and Odell, M. 2009. Cancer prognostication using a recombinant form of the lectin from Helix pomatia agglutinin. Glycobiology. 19 (11), p. 1318.

UEA-1 enables discrimination between prostate specific antigen from patients with prostate cancer and benign prostatic hyperplasia
Dwek, M., Jenks, A. and Leathem, A. 2009. UEA-1 enables discrimination between prostate specific antigen from patients with prostate cancer and benign prostatic hyperplasia. Glycobiology. 19 (11), p. 1318.

Proteome analysis of metastatic colorectal cancer cells recognized by the lectin Helix pomatia agglutinin (HPA)
Saint-Guirons, J., Zeqiraj, E., Schumacher, U., Greenwell, P. and Dwek, M. 2007. Proteome analysis of metastatic colorectal cancer cells recognized by the lectin Helix pomatia agglutinin (HPA). Proteomics. 7 (22), pp. 4082-4089.

Colorectal cancer – a sticky problem
Dwek, M. 2007. Colorectal cancer – a sticky problem. Oncology News. 2 (3), pp. 19-21.

Identification and elimination of false-positives in an ELISA-based system for qualitative assessment of glycoconjugate binding using a selection of plant lectins
Afrough, B., Dwek, M. and Greenwell, P. 2007. Identification and elimination of false-positives in an ELISA-based system for qualitative assessment of glycoconjugate binding using a selection of plant lectins. BioTechniques. 43 (4), pp. 458-462.

Predictors of axillary lymph node metastasis in breast cancer: a systematic review
Patani, N.R., Dwek, M. and Douek, M. 2007. Predictors of axillary lymph node metastasis in breast cancer: a systematic review. European Journal of Surgical Oncology. 33 (4), pp. 409-419.

A proteomic approach to identify the integrins α 6 and α V as HPA binding partners in the metastatic colorectal cancer cell line HT29
Saint-Guirons, J., Zeqiraj, E., Greenwell, P. and Dwek, M. 2006. A proteomic approach to identify the integrins α 6 and α V as HPA binding partners in the metastatic colorectal cancer cell line HT29. Molecular and Cellular Proteomics. 5 (10 (supplement)), p. S148.

Confocal microscopy for the identification of glycosylation changes associated with metastatic colorectal cancer
Zeqiraj, E., Saint-Guirons, J., Kerrigan, M.J.P. and Dwek, M. 2005. Confocal microscopy for the identification of glycosylation changes associated with metastatic colorectal cancer. The Molecular Biology of Colorectal Cancer. UBHT Education Centre, Bristol, UK 10 - 11 Mar 2005

The metabolic role of methymalonyl CoA mutase in Escherichia coli
Kannan, S.M., Dwek, M., Bucke, C. and Roy, I. 2005. The metabolic role of methymalonyl CoA mutase in Escherichia coli. Proceedings of Viteomics: structure and function of vitamins and cofactors. Cambridge, UK 2005

Structure/function of N-glycans
Dwek, M. 2005. Structure/function of N-glycans. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics. 2nd edition Hoboken, USA Wiley.

Glycoproteomics
Dwek, M. 2005. Glycoproteomics. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics. 2nd edition Hoboken, USA Wiley.

Breast cancer proteomics using 2-dimensional gel electrophoresis
Rawlings, S. and Dwek, M. 2004. Breast cancer proteomics using 2-dimensional gel electrophoresis. in: Brooks, S. and Harris, A. (ed.) Breast cancer research protocols New Jersey, USA Humana Press.

Harnessing changes in cellular glycosylation in new cancer treatment strategies
Dwek, M. and Brooks, S. 2004. Harnessing changes in cellular glycosylation in new cancer treatment strategies. Current Cancer Drug Targets. 4 (5), pp. 425-442.

Proteome analysis enables separate clustering of normal breast, benign breast and breast cancer tissues
Dwek, M. and Alaiya, A.A. 2003. Proteome analysis enables separate clustering of normal breast, benign breast and breast cancer tissues. British Journal of Cancer. 89 (2), pp. 305-307.

Glycoproteomics
Dwek, M. and Mills, P. 2003. Glycoproteomics. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics Chichester, UK Wiley.

Structure/function of N-glycans
Brooks, S. and Dwek, M. 2003. Structure/function of N-glycans. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics Chichester, UK Wiley.

Use of proteomic methodology for the characterization of human milk fat globular membrane proteins
Charlwood, J., Hanrahan, S., Tyldesley, R., Langridge, J., Dwek, M. and Camilleri, P. 2002. Use of proteomic methodology for the characterization of human milk fat globular membrane proteins. Analytical Biochemistry. 301 (2), pp. 314-324.

Current perspectives in cancer proteomics
Dwek, M. and Rawlings, S. 2002. Current perspectives in cancer proteomics. Molecular Biotechnology. 22 (2), pp. 139-152.

Functional and molecular glycobiology
Brooks, S., Dwek, M. and Schumacher, U. 2002. Functional and molecular glycobiology. Oxford, UK BIOS Scientific.

Proteome and glycosylation mapping identifies post-translational modifications associated with aggressive breast cancer
Dwek, M., Ross, H. and Leathem, A. 2001. Proteome and glycosylation mapping identifies post-translational modifications associated with aggressive breast cancer. Proteomics. 1 (6), pp. 756-63.

Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer
Dwek, M., Ross, H., Streets, A., Brooks, S., Adam, E., Titcomb, A., Woodside, J., Schumacher, U. and Leathem, A. 2001. Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer. International Journal of Cancer. 95 (2), pp. 79-85.

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