Background
A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored.
Methods
We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.
Results
Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 (conditional p = 2.51 × 10−4; OR = 1.04; 95% CI 1.02–1.07) and rs77928427 (p = 1.86 × 10−4; OR = 1.04; 95% CI 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.
Conclusion
Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.
Impact
Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.
Introduction:
Knowledge transfer in pediatric rehabilitation is challenging and requires active, multifaceted strategies. The use of knowledge brokers (KBs) is one such strategy noted to promote clinician behavior change. The success of using KBs to transfer knowledge relies on their ability to adapt to ever-changing clinical contexts. In addition, with the rapid growth of online platforms as knowledge transfer forums, KBs must become effective in virtual environments. Although the role of KBs has been studied in various clinical contexts, their emerging role in specific online environments designed to support evidence-based behavior change has not yet been described. Our objective is to describe the roles of, and strategies used by, four KBs involved in a virtual community of practice to guide and inform future online KB interventions.
Methods:
A descriptive design guided this study and a thematic content analysis process was used to analyze online KB postings. The Promoting Action on Research in Health Sciences knowledge transfer framework and online andragogical learning theories assisted in the coding. A thematic map was created illustrating the links between KBs' strategies and emerging roles in the virtual environment.
Results:
We analyzed 95 posts and identified three roles: 1) context architect: promoting a respectful learning environment, 2) knowledge sharing promoter: building capacity, and 3) linkage creator: connecting research-to-practice. Strategies used by KBs reflected invitational, constructivism, and connectivism approaches, with roles and strategies changing over time.
Discussion:
This study increases our understanding of the actions of KBs in virtual contexts to foster uptake of research evidence in pediatric physiotherapy. Our results provide valuable information about the knowledge and skills required by individuals to fulfill this role in virtual environments.
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