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- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)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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- Eriksson, A., et al.
(författare)
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A method for estimating the interactions in dissipative particle dynamics from particle trajectories
- 2009
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Ingår i: Journal of Physics Condensed Matter. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 21:9, s. art. no. 095401-
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a method for determining the functional form of the stochastic and dissipative interactions in a dissipative particle dynamics (DPD) model from projected phase space trajectories. The DPD model is viewed as a coarse graining of a detailed dynamics that displays a clear timescale separation. Based on the Mori-Zwanzig projection operator method we derive a consistency equation for the stochastic interaction in DPD. The consistency equation can be solved by an iterative bootstrapping procedure. Combined with standard techniques for estimating the conservative interaction, our method makes it possible to reconstruct all the forces in a coarse-grained DPD model. We demonstrate how the method works by recreating the interactions in a DPD model from its phase space trajectory. Furthermore, we discuss how our method can be used in realistic systems with finite timescale separation.
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- Rehm, J., et al.
(författare)
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Alcohol use disorders in EU countries and Norway : An overview of the epidemiology
- 2005
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Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 15:4, s. 377-388
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Tidskriftsartikel (refereegranskat)abstract
- Based on a systematic literature search and an expert survey, publications after 1990 on prevalence of alcohol use disorders (AUD) in EU countries and Norway were reviewed. The search was restricted to studies using the DSM-IIIR or DSM-IV, or ICD-10, plus validated instruments to assess AUD. Using only representative general population surveys, the weighted median estimates for 12-month prevalence rates for dependence alone are 6.1% for males (arithmetic mean 5.0%; interquartile range 0.4% to 7.5%) and 1.1% for females (arithmetic mean 1.4%; interquartile range 0.1% to 2.1%). Results thus showed, that AUD constitute a high burden of disease in Europe, but there was high variability of prevalence. Men have higher prevalence rates of AUD than women. No clear pictures emerged with respect to age and AUD prevalence, or with respect to urban vs. rural and AUD prevalence. The discussion highlights potential explanations for the high variability of prevalence between countries, and the fact, that AUD constitute only a small part of all alcohol-related harm.
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