| 51. |
- Bethke, Lara, et al.
(författare)
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Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:5, s. 1195-1202
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Tidskriftsartikel (refereegranskat)abstract
- Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.
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| 52. |
- Bethke, Lara, et al.
(författare)
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The Common D302H Variant of CASP8 Is Associated with Risk of Glioma
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:4, s. 987-989
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Tidskriftsartikel (refereegranskat)abstract
- Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor.
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| 53. |
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| 54. |
- Chuang, Shu-Chun, et al.
(författare)
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A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition
- 2011
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Ingår i: European Journal of Cancer. - Oxford : Pergamon. - 0959-8049 .- 1879-0852. ; 47:12, s. 1808-1816
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Tidskriftsartikel (refereegranskat)abstract
- Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/- 1 year), date (+/- 1 year) and time (+/- 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate <= 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI = 0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00-1.38) but not in women (OR = 0.91, 95% CI = 0.78-1.07; p for heterogeneity < 0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.
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| 55. |
- Colmenares, María José, et al.
(författare)
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Thermal processing of primordial pebbles in evolving protoplanetary disks
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 685
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Tidskriftsartikel (refereegranskat)abstract
- During protoplanetary disk formation, dust grains located in the outer disk retain their pristine icy composition, while solids in the inner stellar-heated disk undergo volatile loss. This process may have left a fossil record in Solar System material, showing different nucleosynthetic imprints that have been attributed to different degrees of thermal processing. However, it remains unclear how a large mass fraction of thermally processed inner-disk pebbles is produced and how these grains are subsequently transported throughout the disk. In this work, we numerically investigate the evolution in time of a two-component pebble disk consisting of both pristine pebbles and those that underwent ice sublimation. We find that stellar outbursts exceeding 1000 times the solar luminosity are efficient in thermally altering, through ice sublimation, a large mass fraction of pebbles (around 80%). After the establishment of this initial radial dust composition gradient throughout the disk, the subsequent mixing and inward drift of pristine outer-disk pebbles alter the inner disk bulk composition from processed to more unprocessed in time. Therefore, if processed pebbles without ice mantles have an isotopic composition similar to ureilite meteorites from the inner Solar System, inner-disk minor bodies forming from the early pebble flux (<1 Myr) will be isotopically ureilite-like, while later-formed bodies will be increasingly admixed with the signature of the lateincoming, CI chondrite-like unprocessed pebbles. This appears to be largely consistent with the trend seen between the accretion age of different meteoric classes and their different stable isotope composition anomalies (in μ54Cr, μ48Ca, μ30Si, and μ58Ni), but further work may be needed to explain the role of isotopically anomalous refractory inclusions and anomaly trends in other elements. Our findings further support an early thermal processing of ice mantles via stellar outbursts that are common around young Sun-like stars.
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| 56. |
- Dahlin, Anna M., 1979-, et al.
(författare)
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A genome-wide association study on medulloblastoma
- 2020
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Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
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| 57. |
- Deharo, Jean-Claude, et al.
(författare)
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Perioperative management of antithrombotic treatment during implantation or revision of cardiac implantable electronic devices : the European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI)
- 2016
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 18:5, s. 778-784
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Tidskriftsartikel (refereegranskat)abstract
- The European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI) was a prospective European survey of consecutive adults who had undergone implantation/surgical revision of a cardiac implantable electronic device (CIED) on chronic antithrombotic therapy (enrolment March-June 2015). The aim of the survey was to investigate perioperative treatment with oral anticoagulants and antiplatelets in CIED implantation or surgical revision and to determine the incidence of complications, including clinically significant pocket haematomas. Information on antithrombotic therapy before and after surgery and bleeding and thromboembolic complications occurring after the intervention was collected at first follow-up. The study population comprised 723 patients (66.7% men, 76.9% aged a parts per thousand yen66 years). Antithrombotic treatment was continued during surgery in 489 (67.6%) patients; 6 (0.8%) had their treatment definitively stopped; 46 (6.4%) were switched to another antithrombotic therapy. Heparin bridging was used in 55 out of 154 (35.8%) patients when interrupting vitamin K antagonist (VKA) treatment. Non-vitamin K oral anticoagulant (NOAC) treatment was interrupted in 88.7% of patients, with heparin bridging in 25.6%, but accounted for only 25.3% of the oral anticoagulants used. A total of 108 complications were observed in 98 patients. No intracranial haemorrhage or embolic events were observed. Chronic NOAC treatment before surgery was associated with lower rates of minor pocket haematoma (1.4%; P= 0.042) vs. dual antiplatelet therapy (13.0%), VKA (11.4%), VKA + antiplatelet (9.2%), or NOAC + antiplatelet (7.7%). Similar results were observed for bleeding complications (P= 0.028). Perioperative management of patients undergoing CIED implantation/surgical revision while on chronic antithrombotic therapy varies, with evidence of a disparity between guideline recommendations and practice patterns in Europe. Haemorrhagic complications were significantly less frequent in patients treated with NOACs. Despite this, the incidence of severe pocket haematomas was low.
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| 58. |
- Dobbins, Sara E., et al.
(författare)
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Common variation at 10p12.31 near MLLT10 influences meningioma risk
- 2011
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Ingår i: Nature Genetics. - London : Nature America, Inc.. - 1061-4036 .- 1546-1718. ; 43:9, s. 825-827
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.
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| 59. |
- Duell, Eric J, et al.
(författare)
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Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
- 2013
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Ingår i: Genes & Nutrition. - : Springer Berlin/Heidelberg. - 1555-8932 .- 1865-3499. ; 8:6, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.
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| 60. |
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