Association analysis identifies 65 new breast cancer risk loci

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. 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.We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project, funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie, de la Science et de l’Innovation du Québec’ through Genome Québec, and the Quebec Breast Cancer Foundation; the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH Grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combining of the GWAS data was supported in part by The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative)

Synthesis of Polymer Grafted Magnetite Nanoparticle with the Highest Grafting Density via Controlled Radical Polymerization

The surface-initiated ATRP of benzyl methacrylate, methyl methacrylate, and styrene from magnetite nanoparticle is investigated, without the use of sacrificial (free) initiator in solution. It is observed that the grafting density obtained is related to the polymerization kinetics, being higher for faster polymerizing monomer. The grafting density was found to be nearly 2 chains/nm2for the rapidly polymerizing benzyl methacrylate. In contrast, for the less rapidly polymerizing styrene, the grafting density was found to be nearly 0.7 chain/nm2. It is hypothesized that this could be due to the relative rates of surface-initiated polymerization versus conformational mobility of polymer chains anchored by one end to the surface. An amphiphilic diblock polymer based on 2-hydroxylethyl methacrylate is synthesized from the polystyrene monolayer. The homopolymer and block copolymer grafted MNs form stable dispersions in various solvents. In order to evaluate molecular weight of the polymer that was grafted on to the surface of the nanoparticles, it was degrafted suitably and subjected to gel permeation chromatography analysis. Thermogravimetric analysis, transmission electron microscopy, and Fourier transform infrared spectroscopy were used to confirm the grafting reaction