From candidate gene studies to GWAS and post-GWAS analyses in breast cancer.
There are now more than 90 established breast cancer risk loci, with 57 new ones, revealed through genome-wide-association studies (GWAS) during the last two years. Established high, moderate and low penetrance genetic variants currently explain ∼49% of familial breast cancer risk. GWAS-discovered variants account for 14%, and it is estimated that another 1000 yet-to-be-discovered loci could contribute an additional ∼14% of familial risk. Polygenic risk scores can already be used to stratify breast cancer risk in the female population and could improve the targeting of mammographic screening programmes, which are at present largely based on age-specific risks. Fine-scale mapping and functional analyses are revealing candidate causal variants and the molecular mechanisms by which GWAS-hits may act. Better-powered GWAS and genome-wide sequencing projects are likely to continue identifying new breast cancer causal variants.
Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK; Genomic Medicine Group, CIBERER, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.
Laura
L
Fachal
Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. Electronic address: amd24@medschl.cam.ac.uk.
Alison M
AM
Dunning
D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008327:Mammography; D020641:Polymorphism, Single Nucleotide