METHODS: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.

METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.

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% confidence interval (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 (r(2) ≥ 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.

Methods: A validated questionnaire was sent to 1290 endoscopy personnel globally. Of these, the data of all 330 responders (25.6%) from 15 countries, related to the current recommendations on proper personal protective equipment (PPE), case selection, scope cleaning, and safety perception, were analyzed. Ordinal logistic regression was used to determine the relationships between the variables.

Results: Despite an overwhelming agreement with the recommendations on PPE (94.5%) and case selection (95.5%), their practicality and applicability on PPE recommendations and case selection were significantly lower (p=0.001, p=0.047, p<0.001, and p=0.032, respectively). Factors that were associated with lower sense of safety in endoscopy units were younger age (p=0.004), less working experience (p=0.008), in-training status (p=0.04), and higher national prevalence of COVID-19 (p=0.003). High prevalent countries also had more difficulty implementing the guidelines (p<0.001) and they considered the PPE recommendations less practical and showed lower agreement with them (p<0.001 and p=0.008, respectively). A higher number of in-hospital COVID-19 patients was associated with less agreement with PPE recommendations (p=0.039).

METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.