| 1. |
|
|
| 2. |
- Dareng, EO, et al.
(author)
-
Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
-
In: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
-
Journal article (peer-reviewed)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.
|
|
| 3. |
|
|
| 4. |
- Pearce, Neil E, et al.
(author)
-
IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
-
In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
|
|
| 5. |
|
|
| 6. |
- Conti, David, V, et al.
(author)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 7. |
- Heesen, V., et al.
(author)
-
Calibrating the relation of low-frequency radio continuum to star formation rate at 1 kpc scale with LOFAR
- 2019
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622
-
Journal article (peer-reviewed)abstract
- Radio continuum (RC) emission in galaxies allows us to measure star formation rates (SFRs) unaffected by extinction due to dust, of which the low-frequency part is uncontaminated from thermal (free-free) emission. Aims. We calibrate the conversion from the spatially resolved 140 MHz RC emission to the SFR surface density (ΣSFR) at 1 kpc scale. Radio spectral indices give us, by means of spectral ageing, a handle on the transport of cosmic rays using the electrons as a proxy for GeV nuclei. Methods. We used recent observations of three galaxies (NGC 3184, 4736, and 5055) from the LOFAR Two-metre Sky Survey (LoTSS), and archival LOw-Frequency ARray (LOFAR) data of NGC 5194. Maps were created with the facet calibration technique and converted to radio ΣSFR maps using the Condon relation. We compared these maps with hybrid ΣSFR maps from a combination of GALEX far-ultraviolet and Spitzer 24 μm data using plots tracing the relation at the highest angular resolution allowed by our data at 1.2 × 1.2 kpc 2 resolution. Results. The RC emission is smoothed with respect to the hybrid ΣSFR owing to the transport of cosmic-ray electrons (CREs) away from star formation sites. This results in a sublinear relation (ΣSFR)RC [(ΣSFR)hyb] a , where a = 0.59 ± 0.13 (140 MHz) and a = 0.75 ± 0.10 (1365 MHz). Both relations have a scatter of σ = 0.3 dex. If we restrict ourselves to areas of young CREs (α > -0.65; Iν ν α ), the relation becomes almost linear at both frequencies with a 0.9 and a reduced scatter of σ = 0.2 dex. We then simulate the effect of CRE transport by convolving the hybrid ΣSFR maps with a Gaussian kernel until the RC-SFR relation is linearised; CRE transport lengths are l = 1-5 kpc. Solving the CRE diffusion equation, assuming dominance of the synchrotron and inverse-Compton losses, we find diffusion coefficients of D = (0.13-1.5) × 10 28 cm 2 s -1 at 1 GeV. Conclusions. A RC-SFR relation at 1.4 GHz can be exploited to measure SFRs at redshift z 10 using 140 MHz observations.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
