| 1. |
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| 2. |
- Atwood, W. B., et al.
(författare)
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THE LARGE AREA TELESCOPE ON THE FERMI GAMMA-RAY SPACE TELESCOPE MISSION
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 697:2, s. 1071-1102
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Tidskriftsartikel (refereegranskat)abstract
- The Large Area Telescope (Fermi/LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view (FoV), high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV. The LAT was built by an international collaboration with contributions from space agencies, high-energy particle physics institutes, and universities in France, Italy, Japan, Sweden, and the United States. This paper describes the LAT, its preflight expected performance, and summarizes the key science objectives that will be addressed. On-orbit performance will be presented in detail in a subsequent paper. The LAT is a pair-conversion telescope with a precision tracker and calorimeter, each consisting of a 4 x 4 array of 16 modules, a segmented anticoincidence detector that covers the tracker array, and a programmable trigger and data acquisition system. Each tracker module has a vertical stack of 18 (x, y) tracking planes, including two layers (x and y) of single-sided silicon strip detectors and high-Z converter material (tungsten) per tray. Every calorimeter module has 96 CsI(Tl) crystals, arranged in an eight-layer hodoscopic configuration with a total depth of 8.6 radiation lengths, giving both longitudinal and transverse information about the energy deposition pattern. The calorimeter's depth and segmentation enable the high-energy reach of the LAT and contribute significantly to background rejection. The aspect ratio of the tracker (height/width) is 0.4, allowing a large FoV (2.4 sr) and ensuring that most pair-conversion showers initiated in the tracker will pass into the calorimeter for energy measurement. Data obtained with the LAT are intended to (1) permit rapid notification of high-energy gamma-ray bursts and transients and facilitate monitoring of variable sources, (2) yield an extensive catalog of several thousand high-energy sources obtained from an all-sky survey, (3) measure spectra from 20 MeV to more than 50 GeV for several hundred sources, (4) localize point sources to 0.3-2 arcmin, (5) map and obtain spectra of extended sources such as SNRs, molecular clouds, and nearby galaxies, (6) measure the diffuse isotropic gamma-ray background up to TeV energies, and (7) explore the discovery space for dark matter.
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| 3. |
- Abdo, A. A., et al.
(författare)
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Gamma-ray emission concurrent with the nova in the symbiotic binary V407 cygni
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5993, s. 817-821
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Tidskriftsartikel (refereegranskat)abstract
- Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce x-ray emission, but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable γ-ray emission (0.1 to 10 billion electron volts) from the recently detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary and that particles can be accelerated effectively to produce π0 decay γ-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.
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| 4. |
- Abdo, A. A., et al.
(författare)
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The spectral energy distribution of fermi bright blazars
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 716:1, s. 30-70
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Tidskriftsartikel (refereegranskat)abstract
- We have conducted a detailed investigation of the broadband spectral properties of the gamma-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi gamma-ray spectra with Swift, radio, infra-red, optical, and other hard X-ray/gamma-ray data, collected within 3 months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous spectral energy distributions (SED) for 48 LBAS blazars. The SED of these gamma-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual log nu-log nu F-nu representation, the typical broadband spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SED to characterize the peak intensity of both the low-and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broadband colors (i.e., the radio to optical, alpha(ro), and optical to X-ray, alpha(ox), spectral slopes) and from the gamma-ray spectral index. Our data show that the synchrotron peak frequency (nu(S)(peak)) is positioned between 10(12.5) and 10(14.5) Hz in broad-lined flat spectrum radio quasars (FSRQs) and between 10(13) and 10(17) Hz in featureless BL Lacertae objects. We find that the gamma-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron-inverse Compton scenarios. However, simple homogeneous, one-zone, synchrotron self-Compton (SSC) models cannot explain most of our SED, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. More complex models involving external Compton radiation or multiple SSC components are required to reproduce the overall SED and the observed spectral variability. While more than 50% of known radio bright high energy peaked (HBL) BL Lacs are detected in the LBAS sample, only less than 13% of known bright FSRQs and LBL BL Lacs are included. This suggests that the latter sources, as a class, may be much fainter gamma-ray emitters than LBAS blazars, and could in fact radiate close to the expectations of simple SSC models. We categorized all our sources according to a new physical classification scheme based on the generally accepted paradigm for Active Galactic Nuclei and on the results of this SED study. Since the LAT detector is more sensitive to flat spectrum gamma-ray sources, the correlation between nu(S)(peak) and gamma-ray spectral index strongly favors the detection of high energy peaked blazars, thus explaining the Fermi overabundance of this type of sources compared to radio and EGRET samples. This selection effect is similar to that experienced in the soft X-ray band where HBL BL Lacs are the dominant type of blazars.
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| 5. |
- Abdo, A. A., et al.
(författare)
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FERMI LARGE AREA TELESCOPE FIRST SOURCE CATALOG
- 2010
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 188:2, s. 405-436
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Tidskriftsartikel (refereegranskat)abstract
- We present a catalog of high-energy gamma-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), during the first 11 months of the science phase of the mission, which began on 2008 August 4. The First Fermi-LAT catalog (1FGL) contains 1451 sources detected and characterized in the 100 MeV to 100 GeV range. Source detection was based on the average flux over the 11 month period, and the threshold likelihood Test Statistic is 25, corresponding to a significance of just over 4 sigma. The 1FGL catalog includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and power-law spectral fits as well as flux measurements in five energy bands for each source. In addition, monthly light curves are provided. Using a protocol defined before launch we have tested for several populations of gamma-ray sources among the sources in the catalog. For individual LAT-detected sources we provide firm identifications or plausible associations with sources in other astronomical catalogs. Identifications are based on correlated variability with counterparts at other wavelengths, or on spin or orbital periodicity. For the catalogs and association criteria that we have selected, 630 of the sources are unassociated. Care was taken to characterize the sensitivity of the results to the model of interstellar diffuse gamma-ray emission used to model the bright foreground, with the result that 161 sources at low Galactic latitudes and toward bright local interstellar clouds are flagged as having properties that are strongly dependent on the model or as potentially being due to incorrectly modeled structure in the Galactic diffuse emission.
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| 6. |
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| 7. |
- Abdo, A. A., et al.
(författare)
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The first catalog of active galactic nuclei detected by the Fermi large area telescope
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 715:1, s. 429-457
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Tidskriftsartikel (refereegranskat)abstract
- We present the first catalog of active galactic nuclei (AGNs) detected by the Large Area Telescope (LAT), corresponding to 11 months of data collected in scientific operation mode. The First LAT AGN Catalog (1LAC) includes 671 gamma-ray sources located at high Galactic latitudes (|b| > 10 degrees) that are detected with a test statistic greater than 25 and associated statistically with AGNs. Some LAT sources are associated with multiple AGNs, and consequently, the catalog includes 709 AGNs, comprising 300 BL Lacertae objects, 296 flat-spectrum radio quasars, 41 AGNs of other types, and 72 AGNs of unknown type. We also classify the blazars based on their spectral energy distributions as archival radio, optical, and X-ray data permit. In addition to the formal 1LAC sample, we provide AGN associations for 51 low-latitude LAT sources and AGN "affiliations" (unquantified counterpart candidates) for 104 high-latitude LAT sources without AGN associations. The overlap of the 1LAC with existing gamma-ray AGN catalogs (LBAS, EGRET, AGILE, Swift, INTEGRAL, TeVCat) is briefly discussed. Various properties-such as gamma-ray fluxes and photon power-law spectral indices, redshifts, gamma-ray luminosities, variability, and archival radio luminosities-and their correlations are presented and discussed for the different blazar classes. We compare the 1LAC results with predictions regarding the gamma-ray AGN populations, and we comment on the power of the sample to address the question of the blazar sequence.
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| 8. |
- Ackermann, M., et al.
(författare)
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A STATISTICAL APPROACH TO RECOGNIZING SOURCE CLASSES FOR UNASSOCIATED SOURCES IN THE FIRST FERMI-LAT CATALOG
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 753:1, s. 83-
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Large Area Telescope (LAT) First Source Catalog (1FGL) provided spatial, spectral, and temporal properties for a large number of gamma-ray sources using a uniform analysis method. After correlating with the most-complete catalogs of source types known to emit gamma rays, 630 of these sources are unassociated (i.e., have no obvious counterparts at other wavelengths). Here, we employ two statistical analyses of the primary gamma-ray characteristics for these unassociated sources in an effort to correlate their gamma-ray properties with the active galactic nucleus (AGN) and pulsar populations in 1FGL. Based on the correlation results, we classify 221 AGN-like and 134 pulsar-like sources in the 1FGL unassociated sources. The results of these source classifications appear to match the expected source distributions, especially at high Galactic latitudes. While useful for planning future multiwavelength follow-up observations, these analyses use limited inputs, and their predictions should not be considered equivalent to probable source classes for these sources. We discuss multiwavelength results and catalog cross-correlations to date, and provide new source associations for 229 Fermi-LAT sources that had no association listed in the 1FGL catalog. By validating the source classifications against these new associations, we find that the new association matches the predicted source class in similar to 80% of the sources.
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| 9. |
- Abdo, A. A., et al.
(författare)
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FERMI/LARGE AREA TELESCOPE BRIGHT GAMMA-RAY SOURCE LIST
- 2009
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 183:1, s. 46-66
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Tidskriftsartikel (refereegranskat)abstract
- Following its launch in 2008 June, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in three months produced a deeper and better resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than similar to 10 sigma) gamma-ray sources in these data. These are the best characterized and best localized point-like (i.e., spatially unresolved) gamma-ray sources in the early mission data.
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| 10. |
- Abdo, A. A., et al.
(författare)
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BRIGHT ACTIVE GALACTIC NUCLEI SOURCE LIST FROM THE FIRST THREE MONTHS OF THE FERMI LARGE AREA TELESCOPE ALL-SKY SURVEY
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 700:1, s. 597-622
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Tidskriftsartikel (refereegranskat)abstract
- The first three months of sky-survey operation with the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope reveal 132 bright sources at |b| > 10 degrees with test statistic greater than 100 ( corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES, and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known active galactic nuclei (AGNs). This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely, Centaurus A and NGC 1275, and 104 blazars consisting of 58 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 4 blazars with unknown classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy-peaked BL Lacs (HBLs), sources which were previously difficult to detect in the GeV range. Another 10 lower-confidence associations are found. Only 33 of the sources, plus two at |b| < 10 degrees, were previously detected with Energetic Gamma-Ray Experiment Telescope( EGRET), probably due to variability. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N-log S distributions and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BL Lacs. The contribution of LAT blazars to the total extragalactic gamma-ray intensity is estimated.
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| 11. |
- Abdo, A. A., et al.
(författare)
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FERMI/LARGE AREA TELESCOPE DISCOVERY OF GAMMA-RAY EMISSION FROM THE FLAT-SPECTRUM RADIO QUASAR PKS 1454-354
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 697:1, s. 934-941
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery by the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope of high-energy gamma-ray (GeV) emission from the flat-spectrum radio quasar PKS 1454-354 (z = 1.424). On 2008 September 4, the source rose to a peak flux of (3.5 +/- 0.7) x 10(-6) ph cm(-2) s(-1) (E > 100 MeV) on a timescale of hours and then slowly dropped over the following 2 days. No significant spectral changes occurred during the flare. Fermi/LAT observations also showed that PKS 1454-354 is the most probable counterpart of the unidentified EGRET source 3EG J1500-3509. Multiwavelength measurements performed during the following days (7 September with Swift; 6-7 September with the ground-based optical telescope Automated Telescope for Optical Monitoring; 13 September with the Australia Telescope Compact Array) resulted in radio, optical, UV, and X-ray fluxes greater than archival data, confirming the activity of PKS 1454-354.
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| 12. |
- Ackermann, M., et al.
(författare)
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The Second Catalog of Active Galactic Nuclei Detected by the Fermi Large Area Telescope
- 2011
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 743:2
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Tidskriftsartikel (refereegranskat)abstract
- The second catalog of active galactic nuclei (AGNs) detected by the Fermi Large Area Telescope (LAT) in two years of scientific operation is presented. The second LAT AGN catalog (2LAC) includes 1017 γ-ray sources located at high Galactic latitudes (|b| > 10°) that are detected with a test statistic (TS) greater than 25 and associated statistically with AGNs. However, some of these are affected by analysis issues and some are associated with multiple AGNs. Consequently, we define a Clean Sample which includes 886 AGNs, comprising 395 BL Lacertae objects (BL Lac objects), 310 flat-spectrum radio quasars (FSRQs), 157 candidate blazars of unknown type (i.e., with broadband blazar characteristics but with no optical spectral measurement yet), 8 misaligned AGNs, 4 narrow-line Seyfert 1 (NLS1s), 10 AGNs of other types, and 2 starburst galaxies. Where possible, the blazars have been further classified based on their spectral energy distributions (SEDs) as archival radio, optical, and X-ray data permit. While almost all FSRQs have a synchrotron-peak frequency <1014 Hz, about half of the BL Lac objects have a synchrotron-peak frequency >1015 Hz. The 2LAC represents a significant improvement relative to the first LAT AGN catalog (1LAC), with 52% more associated sources. The full characterization of the newly detected sources will require more broadband data. Various properties, such as γ-ray fluxes and photon power-law spectral indices, redshifts, γ-ray luminosities, variability, and archival radio luminosities and their correlations are presented and discussed for the different blazar classes. The general trends observed in 1LAC are confirmed.
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| 13. |
- Abdo, A. A., et al.
(författare)
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SPECTRAL PROPERTIES OF BRIGHT FERMI-DETECTED BLAZARS IN THE GAMMA-RAY BAND
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 710:2, s. 1271-1285
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Tidskriftsartikel (refereegranskat)abstract
- The gamma-ray energy spectra of bright blazars of the LAT Bright AGN Sample LBAS) are investigated using Fermi-LAT data. Spectral properties hardness, curvature, and variability) established using a data set accumulated over 6 months of operation are presented and discussed for different blazar classes and subclasses: flat spectrum radio quasars (FSRQs), low-synchrotron peaked BLLacs (LSP-BLLacs), intermediate-synchrotron peaked BLLacs (ISP-BLLacs), and high-synchrotron peaked BLLacs (HSP-BLLacs). The distribution of photon index G, obtained from a power-law fit above 100 MeV) is found to correlate strongly with blazar subclass. The change in spectral index from that averaged over the 6 months observing period is < 0.2-0.3 when the flux varies by about an order of magnitude, with a tendency toward harder spectra when the flux is brighter for FSRQs and LSP-BLLacs. A strong departure from a single power-law spectrum appears to be a common feature for FSRQs. This feature is also present for some high-luminosity LSP-BLLacs, and a small number of ISP-BLLacs. It is absent in all LBAS HSP-BLLacs. For 3C 454.3 and AO 0235+164, the two brightest FSRQ source and LSP-BLLac source, respectively, a broken power law (BPL) gives the most acceptable of power law, BPL, and curved forms. The consequences of these findings are discussed.
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| 14. |
- Abdo, A. A., et al.
(författare)
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THE FERMI-LAT HIGH-LATITUDE SURVEY : SOURCE COUNT DISTRIBUTIONS AND THE ORIGIN OF THE EXTRAGALACTIC DIFFUSE BACKGROUND
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 720:1, s. 435-453
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Tidskriftsartikel (refereegranskat)abstract
- This is the first of a series of papers aimed at characterizing the populations detected in the high-latitude sky of the Fermi-LAT survey. In this work, we focus on the intrinsic spectral and flux properties of the source sample. We show that when selection effects are properly taken into account, Fermi sources are on average steeper than previously found (e.g., in the bright source list) with an average photon index of 2.40 +/- 0.02 over the entire 0.1-100 GeV energy band. We confirm that flat spectrum radio quasars have steeper spectra than BL Lacertae objects with an average index of 2.48 +/- 0.02 versus 2.18 +/- 0.02. Using several methods, we build the deepest source count distribution at GeV energies, deriving that the intrinsic source (i.e., blazar) surface density at F-100 >= 10(-9) ph cm(2) s(-1) is 0.12(-0.02)(+0.03) deg(-2). The integration of the source count distribution yields that point sources contribute 16(+/- 1.8)% (+/- 7% systematic uncertainty) of the GeV isotropic diffuse background. At the fluxes currently reached by LAT, we can rule out the hypothesis that pointlike sources (i.e., blazars) produce a larger fraction of the diffuse emission.
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| 15. |
- Abdo, A. A., et al.
(författare)
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Gamma-ray light curves and variability of bright fermi-detected blazars
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 722:1, s. 520-542
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents light curves as well as the first systematic characterization of variability of the 106 objects in the high-confidence Fermi Large Area Telescope Bright AGN Sample (LBAS). Weekly light curves of this sample, obtained during the first 11 months of the Fermi survey (2008 August 4-2009 July 4), are tested for variability and their properties are quantified through autocorrelation function and structure function analysis. For the brightest sources, 3 or 4 day binned light curves are extracted in order to determine power density spectra (PDSs) and to fit the temporal structure of major flares. More than 50% of the sources are found to be variable with high significance, where high states do not exceed 1/4 of the total observation range. Variation amplitudes are larger for flat spectrum radio quasars and low/intermediate synchrotron frequency peaked BL Lac objects. Autocorrelation timescales derived from weekly light curves vary from four to a dozen of weeks. Variable sources of the sample have weekly and 3-4 day bin light curves that can be described by 1/f(alpha) PDS, and show two kinds of gamma-ray variability: (1) rather constant baseline with sporadic flaring activity characterized by flatter PDS slopes resembling flickering and red noise with occasional intermittence and (2)-measured for a few blazars showing strong activity-complex and structured temporal profiles characterized by long-term memory and steeper PDS slopes, reflecting a random walk underlying mechanism. The average slope of the PDS of the brightest 22 FSRQs and of the 6 brightest BL Lacs is 1.5 and 1.7, respectively. The study of temporal profiles of well-resolved flares observed in the 10 brightest LBAS sources shows that they generally have symmetric profiles and that their total duration vary between 10 and 100 days. Results presented here can assist in source class recognition for unidentified sources and can serve as reference for more detailed analysis of the brightest gamma-ray blazars.
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| 16. |
- Ackermann, M., et al.
(författare)
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THE RADIO/GAMMA-RAY CONNECTION IN ACTIVE GALACTIC NUCLEI IN THE ERA OF THE FERMI LARGE AREA TELESCOPE
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 741:1, s. 30-
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed statistical analysis of the correlation between radio and gamma-ray emission of the active galactic nuclei (AGNs) detected by Fermi during its first year of operation, with the largest data sets ever used for this purpose. We use both archival interferometric 8.4 GHz data (from the Very Large Array and ATCA, for the full sample of 599 sources) and concurrent single-dish 15 GHz measurements from the Owens Valley Radio Observatory (OVRO, for a sub sample of 199 objects). Our unprecedentedly large sample permits us to assess with high accuracy the statistical significance of the correlation, using a surrogate data method designed to simultaneously account for common-distance bias and the effect of a limited dynamical range in the observed quantities. We find that the statistical significance of a positive correlation between the centimeter radio and the broadband (E > 100 MeV) gamma-ray energy flux is very high for the whole AGN sample, with a probability of < 10(-7) for the correlation appearing by chance. Using the OVRO data, we find that concurrent data improve the significance of the correlation from 1.6 x 10(-6) to 9.0 x 10(-8). Our large sample size allows us to study the dependence of correlation strength and significance on specific source types and gamma-ray energy band. We find that the correlation is very significant (chance probability < 10(-7)) for both flat spectrum radio quasars and BL Lac objects separately; a dependence of the correlation strength on the considered gamma-ray energy band is also present, but additional data will be necessary to constrain its significance.
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| 17. |
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| 18. |
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| 19. |
- Osorio, A., et al.
(författare)
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Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2 (CIMBA)
- 2009
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 101:12, s. 2048-2054
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Tidskriftsartikel (refereegranskat)abstract
- Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.
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| 20. |
- Antoniou, A. C., et al.
(författare)
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Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
- 2010
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
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Tidskriftsartikel (refereegranskat)abstract
- The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
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| 21. |
- Antoniou, A. C., et al.
(författare)
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Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2009
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Ingår i: Human Molecular Genetics. - [Antoniou, Antonis C.; McGuffog, Lesley; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Pooley, Karen A.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England. [Sinilnikova, Olga M.; Leone, Melanie] Univ Lyon, CNRS, Hosp Civils Lyon,Ctr Leon Berard,UMR5201, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canada Res Chair Oncogenet, Canc Genom Lab, Quebec City, PQ, Canada. Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary] Mayo Clin, Rochester, MN USA. [Peterlongo, Paolo; Peissel, Bernard; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Molecolare, Milan, Italy. [Bonanni, Bernardo; Bernard, Loris] Ist Europeo Oncol, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Aviano, Italy. [Bernard, Loris] Cogentech, Consortium Genom Technol, Milan, Italy. [Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Zikan, Michal] Charles Univ Prague, Dept Biochem & Expt Oncol, Fac Med 1, Prague, Czech Republic. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Greene, Mark H.; Mai, Phuong L.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad; Lejbkowicz, Flavio] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] B Rappaport Fac Med, Haifa, Israel. [Andrulis, Irene L.; Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Gerdes, Anne-Marie; Thomassen, Mads] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, DK-5000 Odense, Denmark. [Sunde, Lone] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Caligo, Maria A.] Univ Pisa, Div Surg Mol & Ultrastructural Pathol, Dept Oncol, Pisa, Italy. [Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy. [Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella; Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Dagan, Efrat; Baruch, Ruth Gershoni] Rambam Med Ctr, Genet Inst, Haifa, Israel. [Harbst, Katja] Lund Univ, Dept Oncol, S-22100 Lund, Sweden. [Barbany-Bustinza, Gisela; Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrenska Univ, Dept Oncol, Gothenburg, Sweden. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Philadelphia, PA 19104 USA. [Osorio, Ana; Benitez, Javier] Ctr Invest Biomed Red Enfermedades Raras CIBERERE, Inst Salud Carlos III, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Blanco, Ignacio] Catalan Inst Oncol ICO, Canc Genet Counseling Program, Barcelona, Spain. [Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, Neuenheimer Feld 580 69120, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Rotterdam Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Devilee, Peter] Dept Genet Epidemiol, Leiden, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Utrecht, Med Ctr, Dept Clin Mol Genet, NL-3508 TC Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van Roozendaal, Cornelis E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Rosalind] Inst Canc Res, Translat Canc Genet Team, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys Hosp, Clin Genet, London SE1 9RT, England. [Davidson, Rosemarie] Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare, NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Hodgson, Shirley] Univ London, Dept Canc Genet, St Georges Hosp, London, England. [Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM U509, Serv Genet Oncol, Paris, France. [Buecher, Bruno] Inst Curie, Dept Genet, Paris, France. [Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Lenoir, Gilbert M.] Inst Cancrol Gustave Roussy, Dept Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, INSERM U946, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Lenoir, Gilbert M.] Inst Cancerol Gustave Roussy, CNRS FRE2939, Villejuif, France. [Sevenet, Nicolas; Longy, Michel] Inst Bergonie, Lab Genet Constitutionnelle, Bordeaux, France. [Longy, Michel] Inst Bergonie, INSERM U916, Bordeaux, France. [Ferrer, Sandra Fert] Hop Hotel Dieu, Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Prieur, Fabienne] CHU St Etienne, Serv Genet Clin Chromosom, St Etienne, France. [Goldgar, David] Univ Utah, Dept Dermatol, Salt Lake City, UT 84112 USA. [Miron, Alexander; Yassin, Yosuf] Dana Farber Canc Inst, Boston, MA 02115 USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Hopper, John L.] Univ Melbourne, Melbourne, Australia. [Terry, Mary Beth] Columbia Univ, New York, NY USA. [Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine] Med Univ Vienna, Div Special Gynecol, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. [Barkardottir, Rosa Bjork] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Evanston NW Healthcare, NorthShore Univ Hlth Syst, Evanston, IL 60201 USA. [Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. [Boggess, John F.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Basil, Jack] St Elizabeth Hosp, Edgewood, KY 41017 USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Blank, Stephanie V.] New York Univ, Sch Med, New York, NY 10016 USA. [Toland, Amanda E.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Montagna, Marco; Casella, Cinzia] IRCCS, Ist Oncologico Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Res Inst, St Petersburg, Russia. [Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Schmutzler, Rita K.; Versmold, Beatrix; Arnold, Norbert] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaeco Oncol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynecol, Munich, Germany. Univ Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, Germany. [Niederacher, Dieter] Univ Duesseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, Dusseldorf, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Suttner, Christian] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Schoenbuchner, Ines] Univ Wurzburg, Inst Human Genet, D-8700 Wurzburg, Germany. [Gadzicki, Dorothea] Med Univ, Inst Cellular & Mol Pathol, Hannover, Germany. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clinico San Carlos 28040, Madrid, Spain. : Oxford University Press. - 0964-6906 .- 1460-2083. ; 18:22, s. 4442-4456
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 × 10-4]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.
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- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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