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- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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- Hagerman, Inger, et al.
(författare)
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Effects on heart rate variability by artificially generated indoor nano-sized particles in a chamber study
- 2014
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 88, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- Background: Airborne particles are associated with increased morbidity and mortality due to respiratory and cardiovascular diseases in polluted areas. There is a growing interest in nano-sized particles with diameter < 100 nm and their potential health effects. Heart rate variability (HRV) is a noninvasive method for cardiovascular risk prediction in high prevalent groups. Aim of study: The aim was to evaluate the impact of nano-sized indoor air particles on HRV for healthy and adult females. Methods: All exposures were performed as controlled chamber experiments with particle exposure from burning candles, terpene + ozone reactions or filtered air in a double-blind cross over design. Twenty-two healthy females were investigated during 10 min periods at different exposures and the reactivity in high frequency (HF) spectral band of HRV were computed. Results: Heart rate was unchanged from baseline values in all groups during all experimental settings. HF power of HRV tended to increase during exposure to particles from burning candle while particles from terpene + ozone reactions tended to decrease HF power. Conclusions: Exposure to nano-sized particles of burning candles or terpene + ozone reactions results in different patterns of heart rate variability, with signs of altered autonomic cardiovascular control. Practical implications: This study indicates that the HRV method may be used for information on physiological responses of exposure to different nano-sized particles and contribute to the understanding of mechanisms behind health effects of particle exposures. (C) 2014 The Authors. Published by Elsevier Ltd.
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- Isaxon, Christina, et al.
(författare)
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A Novel System for Source Characterization and Controlled Human Exposure to Nanoparticle Aggregates Generated During Gas–Metal Arc Welding
- 2013
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 1521-7388 .- 0278-6826. ; 47:1, s. 52-59
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in Undetermined The aim of this study was to achieve a method to perform detailed characterization and human exposure studies of nanosized and nanostructured aerosol particles. The source chosen was mild steel, active gas, arc welding fume. The setup consisted of a generation chamber, where welding can be performed, connected to an airtight stainless steel 22 m(3) exposure chamber. Instrumentation, consisting of a tapered element oscillating microbalance, a scanning mobility particle sizer, and a sampler for electron microscopy and particle-induced X-ray emission analysis was connected to the stainless steel chamber. The feasibility of the system for human exposure studies was evaluated by exposing 31 human volunteers, in groups of three, to a test aerosol containing 1 mg/m(3) welding fumes and to conditioned, filtered air. The results show that an aerosol that accurately represents dilute welding fume exposures that occur in workplaces can be produced in a controlled manner, and that the experimental setup can be used for 6 h, double-blind, exposures of human subjects. Particle mass concentration levels could be varied from <5 mu g/m(3) to more than 1000 mu g/m(3). Fumes from metal active gas welding showed a unimodal size distribution with a mean mobility diameter of 160 nm, transmission electron microscopy showed aggregates with a clearly nanosized structure.
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| 10. |
- Isaxon, Christina, et al.
(författare)
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Realistic indoor nano-aerosols for a human exposure facility
- 2013
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Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 60, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to achieve realistic levels of two different types of aerosols commonly abundant in indoor environments in an experimental chamber intended for human exposure studies and aerosol characterization. The aerosols chosen were particles from candle lights (in particle number dominated by inorganic water soluble particles) and from ozone-terpene reactions (organic particles). The aerosol generation and characterization system consisted of a controlled air tight stainless steel 22 m(3) chamber, to which the generation set-ups were connected. No air could enter or leave the chamber except through a conditioning system by which temperature, relative humidity and air exchange rate could be controlled. Candle smoke aerosol was generated from ten candles burning in a 1.33 m(3) glass and stainless steel chamber. The aerosol was diluted by clean air from the conditioning system before entering the chamber. Terpene vapor was generated by passing pure nitrogen through a glass bottle containing limonene oil. Ozone was generated by a spark discharge using pure O-2, and was added to the ventilation air flow downstream the inlet for terpene vapors and upstream the inlet to the chamber. Both aerosols were characterized with respect to number and mass concentrations, size distribution and chemical composition. Particle number concentration in the size range 10-650 nm could be varied from <10 cm(-3) to more than 900,000 cm(-3) (for candle smoke) or to more than 30,000 cm(-3) (for particles formed in a 160 ppb terpene/40 ppb ozone mixture). Furthermore, the set-ups were evaluated by, for each source, repeating the generation at six three-hour long events. For both aerosols repeatable generations at pre-determined concentration levels, that were stable over time, could be achieved. The results show that realistic concentrations of aerosols from real-world environments could be reproduced in a well-controlled manner and that this set-up could be used both for aerosol characterization and for human exposures. (C) 2013 Elsevier Ltd. All rights reserved.
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