| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Dareng, EO, et al.
(författare)
-
Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
-
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
-
Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Abeysekara, A. U., et al.
(författare)
-
A Luminous and Isolated Gamma-Ray Flare from the Blazar B2 1215+30
- 2017
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 836:2
-
Tidskriftsartikel (refereegranskat)abstract
- B2 1215+30 is a BL-Lac-type blazar that was first detected at TeV energies by the MAGIC atmospheric Cherenkov telescopes and subsequently confirmed by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) observatory with data collected between 2009 and 2012. In 2014 February 08, VERITAS detected a large-amplitude flare from B2. 1215+30 during routine monitoring observations of the blazar 1ES. 1218+304, located in the same field of view. The TeV flux reached 2.4 times the Crab Nebula flux with a variability timescale of <3.6 hr. Multiwavelength observations with Fermi-LAT, Swift, and the Tuorla Observatory revealed a correlated high GeV flux state and no significant optical counterpart to the flare, with a spectral energy distribution where the gamma-ray luminosity exceeds the synchrotron luminosity. When interpreted in the framework of a onezone leptonic model, the observed emission implies a high degree of beaming, with Doppler factor delta > 10, and an electron population with spectral index p < 2.3.
|
|
| 29. |
|
|
| 30. |
- Hakansson, Sara, et al.
(författare)
-
Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
-
Ingår i: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
|
|
