| 1. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 2. |
- Bishop, D. Timothy, et al.
(författare)
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Genome-wide association study identifies three loci associated with melanoma risk
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:8, s. 920-925
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322), 11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 x 10(-7) for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.
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| 3. |
- Dobsicek Trefna, Hana, 1979, et al.
(författare)
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Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements
- 2017
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Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:4, s. 471-482
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Tidskriftsartikel (refereegranskat)abstract
- Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.
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| 4. |
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| 5. |
- Hidding, Bert, et al.
(författare)
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Flooding tolerance and horizontal expansion of wetland plants : facilitation by floating mats?
- 2014
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Ingår i: Aquatic Botany. - : Elsevier BV. - 0304-3770 .- 1879-1522. ; 113, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- Water level fluctuations (WLF) can be important disturbances promoting the diversity of riparian plant communities, but are currently absent from many managed aquatic ecosystems. A lack of WLF is thought to reduce plant diversity and hamper hydrosere succession. However, a positive impact of WLF on plant diversity may crucially depend on nutrient availability and the presence of a potential ecosystem engineer, the floating plant Strati otes abides, that may provide structural support to riparian plants. We tested the interactive effects of 40 cm flooding, presence of S. abides and sediment nutrient availability (N and P) on growth and horizontal expansion of eight wetland plant species in a 10 week experiment. Seven out of eight species showed a significant elongation response to flooding. Compared to stagnant water levels, flooding in combination with high nutrient availability decreased horizontal expansion in two short species and increased it in two tall species, whereas flooding decreased horizontal expansion in two other short species under both nutrient levels. In this 10 week experiment, we observed no effect of S. abides on the measured plant parameters. This experiment shows short-term negative effects of flooding on most of the short species. On the long-term, we hypothesize that improvements in water quality and seedling recruitment due to drawdown may result in net positive effects of WLF in the riparian zone, but as the species that were rare in the field happened to be short, care should be taken to maintain rare species when allowing more WLF.(C) 2013 Elsevier B.V. All rights reserved.
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| 6. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 7. |
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| 8. |
- Strosberg, Jonathan R., et al.
(författare)
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Efficacy of octreotide long-acting repeatable in neuroendocrine tumors : RADIANT-2 placebo arm post hoc analysis
- 2015
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 22:6, s. 933-940
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Tidskriftsartikel (refereegranskat)abstract
- Somatostatin analogues (SSA) have demonstrated antiproliferative activity in addition to efficacy for carcinoid symptom control in functional neuroendocrine tumors (NET). Apost hoc analysis of the placebo arm of the RAD001 In Advanced Neuroendocrine Tumors-2 (RADIANT-2) study was conducted to assess the efficacy of octreotide long-acting repeatable (LAR) on progression-free survival (PFS) and overall survival (OS) estimated using the Kaplan-Meier method. Out of 213 patients randomized to placebo plus octreotide LAR in RADIANT-2, 196 patients with foregut, midgut, or hindgut NETwere considered for present analysis. Of these, 41 patients were SSA-treatment naive and 155 had received SSA therapy before study entry. For SSA-naive patients, median PFS by adjudicated central review was 13.6 (95% CI 8.2-22.7) months. For SSA-naive patients with midgut NET (nZ24), median PFS was 22.2 (95% CI 8.3-29.5) months. For patients who had received SSA previously, the median PFS was 11.1 (95% CI 8.4-14.3) months. Among the SSA-pretreated patients who had midgut NET (nZ119), the median PFS was 12.0 (95% CI 8.4-19.3) months. Median OS was 35.8 (95% CI 32.5-48.9) months for patients in the placebo plus octreotide LAR arm; 50.6 (36.4 -not reached) months for SSA-naive patients and 33.5 (95% CI 27.5-44.7) months for those who had received prior SSA. This post hoc analysis of the placebo arm of the large phase 3 RADIANT-2 study provides data on PFS and OS among patients with progressive NET treated with octreotide therapy.
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