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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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| 2. |
- Connolly, John, et al.
(författare)
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Using MODIS derived fPAR with ground based flux tower measurements to derive the light use efficiency for two Canadian peatlands
- 2009
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 32:6, s. 225-225
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Tidskriftsartikel (refereegranskat)abstract
- We used satellite remote sensing data; fractionof photosynthetically active radiation absorbed by vegetation(fPAR) from the Moderate Resolution Imaging Spectrora-diometer (MODIS) in combination with tower eddy covari-ance and meteorological measurements to characterise theLight Use Efficiency parameter (ε)variability and the maxi-mumε(εmax)for two contrasting Canadian peatlands. Eight-day MODISfPAR data were acquired for the Mer Bleue(2000 to 2003) and Western Peatland (2004). Flux towereddy covariance and meteorological measurements were in-tegrated to the same eight-day time stamps as the MODISfPAR data. A light use efficiency model: GPP =ε×APAR(where GPP is Gross Primary Productivity and APAR is ab-sorbed photosynthetically active radiation) was used to cal-culateε. Theεmaxvalue for each year (2000 to 2003) at theMer Bleue bog ranged from 0.58 g C MJ−1to 0.78 g C MJ−1and was 0.91 g C MJ−1in 2004, for the Western Peatland.The average growing seasonεfor the Mer Bleue bog forthe four year period was 0.35 g C MJ−1and for the West-ern Peatland in 2004 was 0.57 g C MJ−1. The average snowfree period for the Mer Bleue bog over the four years was 0.27 g C MJ−1and for the Western Peatland in 2004 was0.39 g C MJ−1. Using the light use efficiency method wecalculated theεmaxand the annual variability inεfor twoCanadian peatlands. We determined that temperature was agrowth-limiting factor at both sites Vapour Pressure Deficit(VPD) however was not. MODISfPAR is a useful tool forthe characterization ofεat flux tower sites.
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| 3. |
- Risérus, Ulf, et al.
(författare)
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Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men
- 2008
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 57:2, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIEVE-Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPAR delta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS-The PPAR delta agonist (10 mg o.d. GW501516), a comparator PPAR alpha agonist (20 mu g o.d. GW590735)), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS-Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (-30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO, directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS-The PPAR delta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.
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