SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Jenkins David J. A.) "

Search: WFRF:(Jenkins David J. A.)

  • Result 1-50 of 78
Sort/group result
   
EnumerationReferenceCoverFind
1.
  • Kanai, M, et al. (author)
  • 2023
  • swepub:Mat__t
  •  
2.
  • Niemi, MEK, et al. (author)
  • 2021
  • swepub:Mat__t
  •  
3.
  • Joffrin, E., et al. (author)
  • Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
  • 2019
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Research review (peer-reviewed)abstract
    • For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
  •  
4.
  • Abel, I, et al. (author)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Journal article (peer-reviewed)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
  •  
5.
  • Romanelli, F, et al. (author)
  • Overview of the JET results
  • 2011
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Journal article (peer-reviewed)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
  •  
6.
  • Kattge, Jens, et al. (author)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Journal article (peer-reviewed)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
  •  
7.
  • Diakaki, M., et al. (author)
  • Towards the high-accuracy determination of the 238U fission cross section at the threshold region at CERN -€“ n_TOF
  • 2016
  • In: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X.
  • Conference paper (peer-reviewed)abstract
    • The U-238 fission cross section is an international standard beyond 2 MeV where the fission plateau starts. However, due to its importance in fission reactors, this cross-section should be very accurately known also in the threshold region below 2 MeV. The U-238 fission cross section has been measured relative to the U-235 fission cross section at CERN - n_TOF with different detection systems. These datasets have been collected and suitably combined to increase the counting statistics in the threshold region from about 300 keV up to 3 MeV. The results are compared with other experimental data, evaluated libraries, and the IAEA standards.
  •  
8.
  • Paradela, C., et al. (author)
  • High-accuracy determination of the 238U/235U fission cross section ratio up to ~1 GeV at n_TOF at CERN
  • 2015
  • In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 91, s. 024602-
  • Journal article (peer-reviewed)abstract
    • The U238 to U235 fission cross section ratio has been determined at n_TOF up to ≈1 GeV, with two different detection systems, in different geometrical configurations. A total of four datasets has been collected and compared. They are all consistent to each other within the relative systematic uncertainty of 3–4%. The data collected at n_TOF have been suitably combined to yield a unique fission cross section ratio as a function of neutron energy. The result confirms current evaluations up to 200 MeV. Good agreement is also observed with theoretical calculations based on the INCL++/Gemini++ combination up to the highest measured energy. The n_TOF results may help solve a long-standing discrepancy between the two most important experimental datasets available so far above 20 MeV, while extending the neutron energy range for the first time up to ≈1 GeV.
  •  
9.
  • Huyghe, Jeroen R., et al. (author)
  • Discovery of common and rare genetic risk variants for colorectal cancer
  • 2019
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
  • Journal article (peer-reviewed)abstract
    • To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
  •  
10.
  • Schmit, Stephanie L, et al. (author)
  • Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
  • 2019
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
  • Journal article (peer-reviewed)abstract
    • Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
  •  
11.
  • Archambault, Alexi N., et al. (author)
  • Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
  • 2020
  • In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
  •  
12.
  • Hawthorn, F., et al. (author)
  • TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf
  • 2023
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3649-3668
  • Journal article (peer-reviewed)abstract
    • We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M and a radius of 0.67 ± 0.01 R. We obtain photometric follow-up observations with a variety of facilities, and we use these data sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R super-Earth in a 3.82-d orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R mini-Neptune in an 8.60-d orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M, while TOI-836 c has a mass of 9.6 ± 2.6 M. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 min for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.
  •  
13.
  • Chen, Zhishan, et al. (author)
  • Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
  • 2024
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
  •  
14.
  • Huyghe, Jeroen R, et al. (author)
  • Genetic architectures of proximal and distal colorectal cancer are partly distinct
  • 2021
  • In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
  • Journal article (peer-reviewed)abstract
    • Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
  •  
15.
  • Thomas, Minta, et al. (author)
  • Response to Li and Hopper
  • 2021
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 108:3, s. 527-529
  • Journal article (peer-reviewed)
  •  
16.
  • Agirre, Jon, et al. (author)
  • The CCP4 suite: integrative software for macromolecular crystallography
  • 2023
  • In: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
  • Journal article (peer-reviewed)abstract
    • The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
  •  
17.
  • Thomas, Minta, et al. (author)
  • Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
  • 2020
  • In: American Journal of Human Genetics. - Cambridge : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:3, s. 432-444
  • Journal article (peer-reviewed)abstract
    • Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
  •  
18.
  • Jang, Seon-Kyeong, et al. (author)
  • Rare genetic variants explain missing heritability in smoking.
  • 2022
  • In: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:11, s. 1577-1586
  • Journal article (peer-reviewed)abstract
    • Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
  •  
19.
  • Tsilidis, Konstantinos K., et al. (author)
  • Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent : a Mendelian randomization study
  • 2021
  • In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 113:6, s. 1490-1502
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
  •  
20.
  • Law, Philip J., et al. (author)
  • Association analyses identify 31 new risk loci for colorectal cancer susceptibility
  • 2019
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Journal article (peer-reviewed)abstract
    • Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
  •  
21.
  • Osborn, A., et al. (author)
  • TOI-332 b: a super dense Neptune found deep within the Neptunian desert
  • 2023
  • In: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 526:1, s. 548-566
  • Journal article (peer-reviewed)abstract
    • To date, thousands of planets have been discovered, but there are regions of the orbital parameter space that are still bare. An example is the short period and intermediate mass/radius space known as the 'Neptunian desert', where planets should be easy to find but discoveries remain few. This suggests unusual formation and evolution processes are responsible for the planets residing here. We present the discovery of TOI-332 b, a planet with an ultra-short period of 0.78 d that sits firmly within the desert. It orbits a K0 dwarf with an effective temperature of 5251 ± 71 K. TOI-332 b has a radius of R, smaller than that of Neptune, but an unusually large mass of 57.2 ± 1.6 M. It has one of the highest densities of any Neptune-sized planet discovered thus far at g cm-3. A 4-layer internal structure model indicates it likely has a negligible hydrogen-helium envelope, something only found for a small handful of planets this massive, and so TOI-332 b presents an interesting challenge to planetary formation theories. We find that photoevaporation cannot account for the mass-loss required to strip this planet of the Jupiter-like envelope it would have been expected to accrete. We need to look towards other scenarios, such as high-eccentricity migration, giant impacts, or gap opening in the protoplanetary disc, to try and explain this unusual discovery.
  •  
22.
  • Sartelli, Massimo, et al. (author)
  • Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
  • 2023
  • In: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
  • Research review (peer-reviewed)abstract
    • Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
  •  
23.
  • Thomas, Minta, et al. (author)
  • Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
  •  
24.
  • Bien, Stephanie A., et al. (author)
  • Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
  • 2019
  • In: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 138:4, s. 307-326
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n=169) and whole blood (n=922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P=2.2x10(-4), replication P=0.01), and PYGL (discovery P=2.3x10(-4), replication P=6.7x10(-4)). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P<0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.
  •  
25.
  • Figtree, Gemma A., et al. (author)
  • Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors JACC State-of-the-Art Review
  • 2023
  • In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 82:13, s. 1343-1359
  • Research review (peer-reviewed)abstract
    • Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  •  
26.
  • Turtelboom,, et al. (author)
  • The TESS-Keck Survey. XI. Mass Measurements for Four Transiting Sub-Neptunes Orbiting K Dwarf TOI-1246
  • 2022
  • In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 163:6
  • Journal article (peer-reviewed)abstract
    • Multiplanet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V = 11.6, K = 9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31, 5.90, 18.66, and 37.92 days. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97 +/- 0.06 R (circle plus), 2.47 +/- 0.08 R (circle plus), 3.46 +/- 0.09 R (circle plus), and 3.72 +/- 0.16 R (circle plus)) and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1 +/- 1.1 M (circle plus), 8.8 +/- 1.2 M (circle plus), 5.3 +/- 1.7 M (circle plus), and 14.8 +/- 2.3 M (circle plus)). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (P (e)/P ( d ) = 2.03) and exhibit transit-timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only five systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70 +/- 0.24 to 3.21 +/- 0.44 g cm(-3), implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 +/- 3.6 M (circle plus). This planet candidate is exterior to TOI-1246 e, with a candidate period of 93.8 days, and we discuss the implications if it is confirmed to be planetary in nature.
  •  
27.
  • Carreras-Torres, Robert, et al. (author)
  • Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response
  • 2023
  • In: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 315-328
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.IMPACT: These findings can guide potential prevention treatments.
  •  
28.
  • Drew, David A., et al. (author)
  • Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer
  • 2024
  • In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:22
  • Journal article (peer-reviewed)abstract
    • Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
  •  
29.
  • Tian, Yu, et al. (author)
  • Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
  • 2024
  • In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130:10, s. 1687-1696
  • Journal article (peer-reviewed)abstract
    • Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
  •  
30.
  • Zaidi, Syed H., et al. (author)
  • Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
  • 2020
  • In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
  •  
31.
  • Barrett, Jennifer H., et al. (author)
  • Genome-wide association study identifies three new melanoma susceptibility loci
  • 2011
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
  • Journal article (peer-reviewed)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.
  •  
32.
  • Guo, Xingyi, et al. (author)
  • Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects
  • 2020
  • In: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 160:4, s. 1164-1178
  • Journal article (peer-reviewed)abstract
    • Background and Aims: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes.Methods: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted.Results: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis.Conclusions: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.
  •  
33.
  • MacGregor, Stuart, et al. (author)
  • Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3
  • 2011
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1114-1118
  • Journal article (peer-reviewed)abstract
    • We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 x 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 x 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.
  •  
34.
  • Tian, Yu, et al. (author)
  • Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
  • 2022
  • In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:8, s. 1135-1148
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
  •  
35.
  • Thomas, Claire E., et al. (author)
  • Epidemiologic factors in relation to colorectal cancer risk and survival by genotoxic colibactin mutational signature
  • 2024
  • In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 33:4, s. 534-546
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The genotoxin colibactin causes a tumor single-base substitution (SBS) mutational signature, SBS88. It is unknown whether epidemiologic factors' association with colorectal cancer risk and survival differs by SBS88.METHODS: Within the Genetic Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry, we measured SBS88 in 4,308 microsatellite stable/microsatellite instability low tumors. Associations of epidemiologic factors with colorectal cancer risk by SBS88 were assessed using multinomial regression (N = 4,308 cases, 14,192 controls; cohort-only cases N = 1,911), and with colorectal cancer-specific survival using Cox proportional hazards regression (N = 3,465 cases).RESULTS: 392 (9%) tumors were SBS88 positive. Among all cases, the highest quartile of fruit intake was associated with lower risk of SBS88-positive colorectal cancer than SBS88-negative colorectal cancer [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.37-0.76; OR = 0.75, 95% CI 0.66-0.85, respectively, Pheterogeneity = 0.047]. Among cohort studies, associations of body mass index (BMI), alcohol, and fruit intake with colorectal cancer risk differed by SBS88. BMI ≥30 kg/m2 was associated with worse colorectal cancer-specific survival among those SBS88-positive [hazard ratio (HR) = 3.40, 95% CI 1.47-7.84], but not among those SBS88-negative (HR = 0.97, 95% CI 0.78-1.21, Pheterogeneity = 0.066).CONCLUSIONS: Most epidemiologic factors did not differ by SBS88 for colorectal cancer risk or survival. Higher BMI may be associated with worse colorectal cancer-specific survival among those SBS88-positive; however, validation is needed in samples with whole-genome or whole-exome sequencing available.IMPACT: This study highlights the importance of identification of tumor phenotypes related to colorectal cancer and understanding potential heterogeneity for risk and survival.
  •  
36.
  • Carleo, Ilaria, et al. (author)
  • The Multiplanet System TOI-421*
  • 2020
  • In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
  • Journal article (peer-reviewed)abstract
    • We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
  •  
37.
  • Jarvik, Gail P., et al. (author)
  • Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis
  • 2020
  • In: Human Genetics and Genomics Advances. - : Cell press. - 2666-2477. ; 1:1
  • Journal article (peer-reviewed)abstract
    • Homozygotes for the higher penetrance hemochromatosis risk allele, HFE c.845G>A (p.Cys282Tyr, or C282Y), have been reported to be at a 2- to 3-fold increased risk for colorectal cancer (CRC). These results have been reported for small sample size studies with no information about age at diagnosis for CRC. An association with age at diagnosis might alter CRC screening recommendations. We analyzed two large European ancestry datasets to assess the association of HFE genotype with CRC risk and age at CRC diagnosis. The first dataset included 59,733 CRC or advanced adenoma cases and 72,351 controls from a CRC epidemiological study consortium. The second dataset included 13,564 self-reported CRC cases and 2,880,218 controls from the personal genetics company, 23andMe. No association of the common hereditary hemochromatosis (HH) risk genotype and CRC was found in either dataset. The odds ratios (ORs) for the association of CRC and HFE C282Y homozygosity were 1.08 (95% confidence interval [CI], 0.91–1.29; p = 0.4) and 1.01 (95% CI, 0.78–1.31, p = 0.9) in the two cohorts, respectively. Age at CRC diagnosis also did not differ by HFE C282Y/C282Y genotype in either dataset. These results indicate no increased CRC risk in individuals with HH genotypes and suggest that persons with HH risk genotypes can follow population screening recommendations for CRC.
  •  
38.
  •  
39.
  • Papadimitriou, Nikos, et al. (author)
  • Body size and risk of colorectal cancer molecular defined subtypes and pathways : mendelian randomization analyses
  • 2024
  • In: EBioMedicine. - : Elsevier. - 2352-3964. ; 101
  • Journal article (peer-reviewed)abstract
    • Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.
  •  
40.
  • Aglago, Elom K., et al. (author)
  • A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
  • 2023
  • In: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
  • Journal article (peer-reviewed)abstract
    • Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
  •  
41.
  • Arun, K. G., et al. (author)
  • New horizons for fundamental physics with LISA
  • 2022
  • In: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
  • Research review (peer-reviewed)abstract
    • The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
  •  
42.
  • Dunlop, Malcolm G, et al. (author)
  • Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations
  • 2012
  • In: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
  •  
43.
  • Iles, Mark M., et al. (author)
  • A variant in FTO shows association with melanoma risk not due to BMI
  • 2013
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
  • Journal article (peer-reviewed)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.
  •  
44.
  • Stacey, Simon N, et al. (author)
  • A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
  • 2011
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
  • Journal article (peer-reviewed)abstract
    • To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
  •  
45.
  • Baird, Denis A., et al. (author)
  • Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
  • 2019
  • In: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
  • Journal article (peer-reviewed)abstract
    • We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2  > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
  •  
46.
  • Bard-Chapeau, Emilie A, et al. (author)
  • Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model.
  • 2014
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:1
  • Journal article (peer-reviewed)abstract
    • The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC, we performed a near-saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human HCC, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC.
  •  
47.
  • Chen, Hongjie, et al. (author)
  • Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals
  • 2021
  • In: Human Genetics and Genomics Advances. - : Cell Press. - 2666-2477. ; 2:3
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.
  •  
48.
  • Harlid, Sophia, 1978-, et al. (author)
  • Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases
  • 2022
  • In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:3, s. 348-360
  • Journal article (peer-reviewed)abstract
    • Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
  •  
49.
  • Kuzuhara, Masayuki, et al. (author)
  • Gliese 12 b: A Temperate Earth-sized Planet at 12 pc Ideal for Atmospheric Transmission Spectroscopy
  • 2024
  • In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 969:1
  • Journal article (peer-reviewed)abstract
    • Recent discoveries of Earth-sized planets transiting nearby M dwarfs have made it possible to characterize the atmospheres of terrestrial planets via follow-up spectroscopic observations. However, the number of such planets receiving low insolation is still small, limiting our ability to understand the diversity of the atmospheric composition and climates of temperate terrestrial planets. We report the discovery of an Earth-sized planet transiting the nearby (12 pc) inactive M3.0 dwarf Gliese 12 (TOI-6251) with an orbital period (P(or)b) of 12.76 days. The planet, Gliese 12 b, was initially identified as a candidate with an ambiguous P-orb from TESS data. We confirmed the transit signal and P-orb using ground-based photometry with MuSCAT2 and MuSCAT3, and validated the planetary nature of the signal using high-resolution images from Gemini/NIRI and Keck/NIRC2 as well as radial velocity (RV) measurements from the InfraRed Doppler instrument on the Subaru 8.2 m telescope and from CARMENES on the CAHA 3.5 m telescope. X-ray observations with XMM-Newton showed the host star is inactive, with an X-ray-to-bolometric luminosity ratio of log L-X/L-bol approximate to - 5.7. Joint analysis of the light curves and RV measurements revealed that Gliese 12 b has a radius of 0.96 +/- 0.05 R-circle plus, a 3 sigma mass upper limit of 3.9M(circle plus), and an equilibrium temperature of 315 +/- 6 K assuming zero albedo. The transmission spectroscopy metric (TSM) value of Gliese 12 b is close to the TSM values of the TRAPPIST-1 planets, adding Gliese 12 b to the small list of potentially terrestrial, temperate planets amenable to atmospheric characterization with JWST.
  •  
50.
  • Lorenzen, Eline D., et al. (author)
  • Species-specific responses of Late Quaternary megafauna to climate and humans
  • 2011
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 479:7373, s. 359-364
  • Journal article (peer-reviewed)abstract
    • Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-50 of 78
Type of publication
journal article (68)
research review (7)
conference paper (1)
Type of content
peer-reviewed (73)
other academic/artistic (3)
Author/Editor
Jenkins, Mark A. (28)
Hoffmeister, Michael (26)
Newcomb, Polly A. (26)
Chang-Claude, Jenny (25)
Brenner, Hermann (25)
Berndt, Sonja I (24)
show more...
Moreno, Victor (24)
Peters, Ulrike (24)
Campbell, Peter T. (24)
Chan, Andrew T. (23)
Giles, Graham G (22)
Casey, Graham (22)
Gruber, Stephen B. (22)
Gunter, Marc J. (22)
van Guelpen, Bethany (21)
Hsu, Li (21)
Li, Li (20)
White, Emily (20)
Wolk, Alicja (19)
Buchanan, Daniel D. (19)
Murphy, Neil (19)
Bishop, D Timothy (18)
Figueiredo, Jane C. (18)
Harrison, Tabitha A. (18)
Huyghe, Jeroen R. (18)
Slattery, Martha L. (18)
Ulrich, Cornelia M. (18)
Woods, Michael O. (18)
Le Marchand, Loïc (18)
Gsur, Andrea (17)
Potter, John D. (17)
Rennert, Gad (17)
Conti, David V (16)
Albanes, Demetrius (16)
Thibodeau, Stephen N (16)
Qu, Conghui (16)
Ogino, Shuji (16)
Sakoda, Lori C. (16)
Schoen, Robert E. (16)
Wu, Anna H. (16)
Lin, Yi (15)
Keku, Temitope O. (15)
Platz, Elizabeth A. (15)
Su, Yu-Ru (15)
Lindblom, Annika (15)
Arndt, Volker (14)
Visvanathan, Kala (14)
Schmit, Stephanie L. (13)
Hopper, John L. (13)
Offit, Kenneth (13)
show less...
University
Karolinska Institutet (27)
Uppsala University (26)
Umeå University (24)
Chalmers University of Technology (14)
Lund University (11)
University of Gothenburg (9)
show more...
Stockholm University (5)
Royal Institute of Technology (3)
Swedish University of Agricultural Sciences (3)
University West (1)
Linköping University (1)
Karlstad University (1)
show less...
Language
English (78)
Research subject (UKÄ/SCB)
Medical and Health Sciences (46)
Natural sciences (26)
Engineering and Technology (3)
Agricultural Sciences (1)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view