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- Garcia-Closas, Montserrat, et al.
(author)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Journal article (peer-reviewed)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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- Cox, Angela, et al.
(author)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Journal article (peer-reviewed)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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- Amata, E., et al.
(author)
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Experimental study of nonlinear interaction of plasma flow with charged thin current sheets : 1. Boundary structure and motion
- 2006
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In: Nonlinear processes in geophysics. - 1023-5809 .- 1607-7946. ; 13:4, s. 365-376
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Journal article (peer-reviewed)abstract
- We study plasma transport at a thin magnetopause (MP), described hereafter as a thin current sheet (TCS), observed by Cluster at the southern cusp on 13 February 2001 around 20:01 UT. The Cluster observations generally agree with the predictions of the Gas Dynamic Convection Field (GDCF) model in the magnetosheath (MSH) up to the MSH boundary layer, where significant differences are seen. We find for the MP a normal roughly along the GSE x-axis, which implies a clear departure from the local average MP normal, a similar to 90 km thickness and an outward speed of 35 km/s. Two populations are identified in the MSH boundary layer: the first one roughly perpendicular to the MSH magnetic field, which we interpret as the "incident" MSH plasma, the second one mostly parallel to B. Just after the MP crossing a velocity jet is observed with a peak speed of 240 km/s, perpendicular to B, with M-A=3 and beta> 10 (peak value 23). The magnetic field clock angle rotates by 70 degrees across the MP. E-x is the main electric field component on both sides of the MP, displaying a bipolar signature, positive on the MSH side and negative on the opposite side, corresponding to a similar to 300 V electric potential jump across the TCS. The E x B velocity generally coincides with the perpendicular velocity measured by CIS; however, in the speed jet a difference between the two is observed, which suggests the need for an extra flow source. We propose that the MP TCS can act locally as an obstacle for low-energy ions (<350 eV), being transparent for ions with larger gyroradius. As a result, the penetration of plasma by finite gyroradius is considered as a possible source for the jet. The role of reconnection is briefly discussed. The electrodynamics of the TCS along with mass and momentum transfer across it are further discussed in the companion paper by Savin et al. (2006).
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- Kostova, Nora, et al.
(author)
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Immunohistochemical demonstration of histone H10 in human breast carcinoma
- 2005
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In: Histochemistry and Cell Biology. - : Springer Science and Business Media LLC. - 0948-6143 .- 1432-119X. ; 124:5, s. 435-443
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Journal article (peer-reviewed)abstract
- Histone H10 is a linker histone subvariant present in tissues of low proliferation rate. It is supposed to participate in the expression and maintenance of the terminal differentiation phenotype. The aim of this work was to study histone H10 distribution in human breast carcinoma and its relationship with the processes of proliferation and differentiation. Most of the cells in carcinomas of moderate and high level of differentiation expressed histone H10 including cells invading connective and adipose tissues. In low differentiated tumours, the number of H10 expressing cells was considerably lower. Staining of myoepithelial cells, when seen, and of stromal fibroblasts was variable. The metastatic malignant cells in the lymph nodes also accumulated H10 but lymphocytes were always negative. All immunopositive malignant cells exhibited signs of polymorphism. Double H1 0/Ki-67 staining showed that the growth fraction in more differentiated tumours belonged to the H10-positive cells, while in poorly differentiated carcinomas it also included a cell subpopulation not expressing H10. If expressed, p27Kip1 was always found in H10-positive cells. These findings are inconsistent with the widespread view that histone H10 is expressed only in terminally differentiated cells. Rather, they suggest that the protein is expressed in cells in a prolonged intermitotic period irrespective of their level of differentiation. Double H10/Ki-67 immunostaining could be a useful tool in studying the growth fraction in tumours. © Springer-Verlag 2005.
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- Lebedev, A.A., et al.
(author)
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Highly doped p-type 3C-SiC on 6H-SiC substrates
- 2008
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In: Semiconductor Science and Technology. - : IOP Publishing. - 0268-1242 .- 1361-6641. ; 23:7
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Journal article (peer-reviewed)abstract
- Highly doped p-3C-SiC layers of good crystal perfection have been grown by sublimation epitaxy in vacuum. Analysis of the photoluminescence spectra and temperature dependence of the carrier concentration shows that at least two types of acceptor centers at ∼EV + 0.25 eV and at EV + 0.06-0.07 eV exist in the samples studied. A conclusion is reached that layers of this kind can be used as p-emitters in 3C-SiC devices. © 2008 IOP Publishing Ltd.
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| 10. |
- Lebedev, S.P., et al.
(author)
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P-type 3C-SiC Grown by Sublimation Epitaxy on 6H-SiC Substrates
- 2009
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In: ECSCRM2008,2008. - Materials Science Forum Vols. 615-617 : Trans Tech Publications. - 9780878493340 ; , s. 177-180
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Conference paper (peer-reviewed)abstract
- Highly doped p-3C-SiC layers of good crystal perfection have been grown by sublimation epitaxy in vacuum. Analysis of the photoluminescence (PL) spectra and temperature dependence of the carrier concentration shows that at least two types of acceptor centers at ~EV + 0.25 eV and at EV + 0.06-0.07 eV exist in the samples studied. A conclusion is made that layers of this kind can be used as p-emitters in 3C-SiC devices.
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