Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

H Zhang; TU Ahearn; J Lecarpentier; D Barnes; J Beesley; G Qi; X Jiang; TA O’Mara; N Zhao; MK Bolla; AM Dunning; J Dennis; Q Wang; ZA Ful; K Aittomäki; IL Andrulis; H Anton-Culver; V Arndt; KJ Aronson; BK Arun; PL Auer; J Azzollini; D Barrowdale; H Becher; MW Beckmann; S Behrens; J Benitez; M Bermisheva; K Bialkowska; A Blanco; C Blomqvist; NV Bogdanova; SE Bojesen; B Bonanni; D Bondavalli; A Borg; H Brauch; H Brenner; I Briceno; A Broeks; SY Brucker; T Brüning; B Burwinkel; SS Buys; H Byers; T Caldés; MA Caligo; M Calvello; D Campa; JE Castelao; J Chang-Claude; SJ Chanock; M Christiaens; H Christiansen; WK Chung; KBM Claes; CL Clarke; S Cornelissen; FJ Couch; A Cox; SS Cross; K Czene; MB Daly; P Devilee; O Diez; SM Domchek; T Dörk; M Dwek; DM Eccles; AB Ekici; DG Evans; PA Fasching; J Figueroa; L Foretova; F Fostira; E Friedman; D Frost; M Gago-Dominguez; SM Gapstur; J Garber; JA García-Sáenz; MM Gaudet; SA Gayther; GG Giles; AK Godwin; MS Goldberg; DE Goldgar; A González-Neira; MH Greene; J Gronwald; P Guénel; L Häberle; E Hahnen; CA Haiman; CR Hake; P Hall; U Hamann; EF Harkness; BAM Heemskerk-Gerritsen; P Hillemanns

Journal article

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

H Zhang, TU Ahearn, J Lecarpentier, D Barnes, J Beesley, G Qi, X Jiang, TA O’Mara, N Zhao, MK Bolla, AM Dunning, J Dennis, Q Wang, ZA Ful, K Aittomäki, IL Andrulis, H Anton-Culver, V Arndt, KJ Aronson, BK Arun Show all

Nature Genetics | NATURE RESEARCH | Published : 2020

DOI: 10.1038/s41588-020-0609-2

Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1–3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10−8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five lo..

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University of Melbourne Researchers

Graham Giles Author

Paul James Author

Robert MacInnis Author

Catriona McLean Author

Related Projects (2)

PRECISION PREVENTION – FROM PRIORITY TO REALITY

THE KATHLEEN CUNINGHAM FOUNDATION CONSORTIUM FOR RESEARCH INTO FAMILIAL BREAST CANCER (KCONFAB)

Grants

Awarded by Odense Universitetshospital

Funding Acknowledgements

We thank all of the individuals who took part in these studies, and all of the researchers, clinicians, technicians and administrative staff who enabled this work to be carried out. This project has been funded in part with Federal funds from the National Cancer Institute Intramural Research Program, National Institutes of Health. Genotyping for the OncoArray was funded by the government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie et de la Science et de l'Innovation du Quebec through Genome Quebec, the Quebec Breast Cancer Foundation for the PERSPECTIVE project, the US National Institutes of Health (NIH) (1U19 CA148065 for the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project and X01HG007492 to the Center for Inherited Disease Research under contract HHSN268201200008I), Cancer Research UK (C1287/A16563), the Odense University Hospital Research Foundation (Denmark), the National R&D Program for Cancer Control-Ministry of Health and Welfare (Republic of Korea; 1420190), the Italian Association for Cancer Research (AIRC; IG16933), the Breast Cancer Research Foundation, the National Health and Medical Research Council (Australia) and German Cancer Aid (110837). Genotyping for the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C1287/A10118 and C12292/A11174), NIH grants (CA128978, CA116167 and CA176785) and the Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 (GAME-ON initiative)), an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Ministere de l'Economie, Innovation et Exportation du Quebec (PSR-SIIRI-701), the Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. Combination of the GWAS data was supported in part by the NIH Cancer Post-Cancer GWAS initiative (1U19 CA148065) (DRIVE, part of the GAME-ON initiative). Linkage disequilibrium score regression analysis was supported by grant CA194393. BCAC was funded by Cancer Research UK (C1287/A16563) and by the European Union via its Seventh Framework Programme (HEALTH-F2-2009-223175; COGS) and the Horizon 2020 Research and Innovation Programme (633784 (B-CAST) and 634935 (BRIDGES)). CIMBA was funded by Cancer Research UK (C12292/A20861 and C12292/A11174). N.C. was funded by NHGRI (1R01 HG010480-01). For a full description of funding and acknowledgments, see the Supplementary Note.