期刊
NATURE
卷 551, 期 7678, 页码 92-+出版社
NATURE PORTFOLIO
DOI: 10.1038/nature24284
关键词
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资金
- PERSPECTIVE project
- Government of Canada through Genome Canada
- Canadian Institutes of Health Research
- Ministere de l'Economie, de la Science et de l'Innovation du Quebec' through Genome Quebec
- Quebec Breast Cancer Foundation
- NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative
- Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH) [U19 CA148065, X01HG007492]
- Cancer Research UK [C1287/A10118, C1287/A16563, C1287/A10710]
- European Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]
- European Union's Horizon 2020 Research and Innovation Programme [633784, 634935]
- European Union [HEALTH-F2-2009-223175]
- Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program
- Ministry of Economic Development, Innovation and Export Trade of Quebec [PSR-SIIRI-701]
- National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative [U19 CA 148065]
- MRC [MC_PC_14105] Funding Source: UKRI
- Cancer Foundation Finland sr [160099, 150147, 110135, 130168] Funding Source: researchfish
- Cancer Research UK [19187, 16561, 15106, 16563, 10118, 20861, 20411] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10124] Funding Source: researchfish
- National Breast Cancer Foundation [PRAC-13-04, IF-12-06, IF-16-002, PF-11-20, PRAC-17-004] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [16H06277] Funding Source: KAKEN
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 ancestry(1). We identified 65 new loci that are associated with overall breast cancer risk at P < 5 x 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.
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