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Background: Breast cancer (BC) screening with mammography reduces mortality but considers currently only age as a risk factor. Personalized risk-based screening has been proposed as a more efficient alternative. For that, risk prediction tools are necessary. Genome-wide association studies have identified numerous genetic variants (single-nucleotide polymorphisms [SNPs]) associated with BC. The effects of SNPs are combined into a polygenic risk score (PRS) as a risk prediction tool. Objectives: We aimed to develop a clinical-grade PRS test suitable for BC risk-stratified screening with clinical recommendations and implementation in clinical practice. Design and methods: In the first phase of our study, we gathered previously published PRS models for predicting BC risk from the literature and validated them using the Estonian Biobank and UK Biobank data sets. We selected the best performing model based on prevalent data and independently validated it in both incident data sets. We then conducted absolute risk simulations, developed risk-based recommendations, and implemented the PRS test in clinical practice. In the second phase, we carried out a retrospective analysis of the PRS test's performance results in clinical practice. Results: The best performing PRS included 2803 SNPs. The C-index of the Cox regression model associating BC status with PRS was 0.656 (SE = 0.05) with a hazard ratio of 1.66. The PRS can stratify individuals with more than a 3-fold risk increase. A total of 2637 BC PRS tests have been performed for women between the ages 30 and 83. Results in clinical use overlap well with expected PRS performance with 5.7% of women with more than 2-fold and 1.4% with more than 3-fold higher risk than the population average. Conclusion: The PRS test separates different BC risk levels and is feasible to implement in clinical practice. [ABSTRACT FROM AUTHOR]

The H1N1 influenza strain Mexico 2009 (H1N1pandemic09) led to mild symptoms (with no or low fever) in Estonia during the 2009-2010 outbreak. Due to the lack of clinical signs, it was difficult to estimate the real spreading of this influenza virus in Estonia and no cases of H1N1 influenza were officially registered in animals either. We used an ELISA method to screen blood sample collections for the presence of anti-H1N1 and anti-H3N2 antibodies. All sera were also tested with the hemagglutination inhibition (HI) assay. Out of the 123 samples from human patients, 23 (i.e. 18.7%) were seropositive for the H1N1pandemic09 virus. In addition, blood samples from six persons were positive for both H1N1 and H3N2 viruses, while according to the data from the Estonian Health Board, people aged 15-65 had a general disease rate of around 3.9%. Almost all of the tested animals from two herds (out of four studied) were seropositive for H1N1pandemic09. The seven HA protein sequences isolated from Estonia were aligned with a consensus sequence of the pandemic H1N1 HA sequences from Mexico using Clusta1W, and 12 amino acids substitutions were found. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) screening with mammography reduces mortality but considers currently only age as a risk factor. Personalized risk-based screening has been proposed as a more efficient alternative. For that, risk prediction tools are necessary. Genome-wide association studies have identified numerous genetic variants (single-nucleotide polymorphisms [SNPs]) associated with BC. The effects of SNPs are combined into a polygenic risk score (PRS) as a risk prediction tool., Objectives: We aimed to develop a clinical-grade PRS test suitable for BC risk-stratified screening with clinical recommendations and implementation in clinical practice., Design and Methods: In the first phase of our study, we gathered previously published PRS models for predicting BC risk from the literature and validated them using the Estonian Biobank and UK Biobank data sets. We selected the best performing model based on prevalent data and independently validated it in both incident data sets. We then conducted absolute risk simulations, developed risk-based recommendations, and implemented the PRS test in clinical practice. In the second phase, we carried out a retrospective analysis of the PRS test's performance results in clinical practice., Results: The best performing PRS included 2803 SNPs. The C-index of the Cox regression model associating BC status with PRS was 0.656 (SE = 0.05) with a hazard ratio of 1.66. The PRS can stratify individuals with more than a 3-fold risk increase. A total of 2637 BC PRS tests have been performed for women between the ages 30 and 83. Results in clinical use overlap well with expected PRS performance with 5.7% of women with more than 2-fold and 1.4% with more than 3-fold higher risk than the population average., Conclusion: The PRS test separates different BC risk levels and is feasible to implement in clinical practice., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BC PRS test AnteBC has been developed by health technology company OÜ Antegenes. AnteBC is registered as a medical device (IVD) in Estonian Medical Devices Database (EMDDB code: 14726). Peeter Padrik, Tõnis Tasa, Berit Kolk, and Neeme Tõnisson have ownership in OÜ Antegenes., (© The Author(s) 2023.)