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- 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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| 6. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 7. |
- Wetzel, G., et al.
(författare)
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Validation of MIPAS-ENVISAT H2O operational data collected between July 2002 and March 2004
- 2013
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:11, s. 5791-5811
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Tidskriftsartikel (refereegranskat)abstract
- Water vapour (H2O) is one of the operationally retrieved key species of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument aboard the Environmental Satellite (ENVISAT) which was launched into its sun-synchronous orbit on 1 March 2002 and operated until April 2012. Within the MIPAS validation activities, independent observations from balloons, aircraft, satellites, and ground-based stations have been compared to European Space Agency (ESA) version 4.61 operational H2O data comprising the time period from July 2002 until March 2004 where MIPAS measured with full spectral resolution. No significant bias in the MIPAS H2O data is seen in the lower stratosphere (above the hygropause) between about 15 and 30 km. Differences of H2O quantities observed by MIPAS and the validation instruments are mostly well within the combined total errors in this altitude region. In the upper stratosphere (above about 30 km), a tendency towards a small positive bias (up to about 10 %) is present in the MIPAS data when compared to its balloon-borne counterpart MIPAS-B, to the satellite instruments HALOE (Halogen Occultation Experiment) and ACE-FTS (Atmospheric Chemistry Experiment, Fourier Transform Spectrometer), and to the millimeter-wave airborne sensor AMSOS (Airborne Microwave Stratospheric Observing System). In the mesosphere the situation is unclear due to the occurrence of different biases when comparing HALOE and ACE-FTS data. Pronounced deviations between MIPAS and the correlative instruments occur in the lowermost stratosphere and upper troposphere, a region where retrievals of H2O are most challenging. Altogether it can be concluded that MIPAS H2O profiles yield valuable information on the vertical distribution of H2O in the stratosphere with an overall accuracy of about 10 to 30% and a precision of typically 5 to 15% - well within the predicted error budget, showing that these global and continuous data are very valuable for scientific studies. However, in the region around the tropopause retrieved MIPAS H2O profiles are less reliable, suffering from a number of obstacles such as retrieval boundary and cloud effects, sharp vertical discontinuities, and frequent horizontal gradients in both temperature and H2O volume mixing ratio (VMR). Some profiles are characterized by retrieval instabilities.
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