PubMed | Karolinska Institutet, Danish Cancer Society, Ontario Health Study, International Agency for Research on Cancer IARC and 58 more.
Type: Journal Article | Journal: Human molecular genetics | Year: 2016
Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
Kowald G.R.,University of Warwick |
Sturzenbaum S.R.,Center for Environment and Health |
Sturzenbaum S.R.,King's College London |
Blindauer C.A.,University of Warwick
International Journal of Molecular Sciences | Year: 2016
Earthworms express, as most animals, metallothioneins (MTs)-small, cysteine-rich proteins that bind d10 metal ions (Zn(II), Cd(II), or Cu(I)) in clusters. Three MT homologues are known for Lumbricus rubellus, the common red earthworm, one of which, wMT-2, is strongly induced by exposure of worms to cadmium. This study concerns composition, metal binding affinity and metal-dependent protein folding of wMT-2 expressed recombinantly and purified in the presence of Cd(II) and Zn(II). Crucially, whilst a single Cd7wMT-2 species was isolated from wMT-2-expressing E. coli cultures supplemented with Cd(II), expressions in the presence of Zn(II) yielded mixtures. The average affinities of wMT-2 determined for either Cd(II) or Zn(II) are both within normal ranges for MTs; hence, differential behaviour cannot be explained on the basis of overall affinity. Therefore, the protein folding properties of Cd- and Zn-wMT-2 were compared by3H NMR spectroscopy. This comparison revealed that the protein fold is better defined in the presence of cadmium than in the presence of zinc. These differences in folding and dynamics may be at the root of the differential behaviour of the cadmium- and zinc-bound protein in vitro, and may ultimately also help in distinguishing zinc and cadmium in the earthworm in vivo. © 2016 by the authors; licensee MDPI, Basel, Switzerland.
Ashworth D.C.,Center for Environment and Health |
Fuller G.W.,King's College London |
Toledano M.B.,Center for Environment and Health |
Font A.,King's College London |
And 3 more authors.
Journal of Environmental and Public Health | Year: 2013
Background. Research to date on health effects associated with incineration has found limited evidence of health risks, but many previous studies have been constrained by poor exposure assessment. This paper provides a comparative assessment of atmospheric dispersion modelling and distance from source (a commonly used proxy for exposure) as exposure assessment methods for pollutants released from incinerators. Methods. Distance from source and the atmospheric dispersion model ADMS-Urban were used to characterise ambient exposures to particulates from two municipal solid waste incinerators (MSWIs) in the UK. Additionally an exploration of the sensitivity of the dispersion model simulations to input parameters was performed. Results. The model output indicated extremely low ground level concentrations of PM10, with maximum concentrations of <0.01 g/m3. Proximity and modelled PM10 concentrations for both MSWIs at postcode level were highly correlated when using continuous measures (Spearman correlation coefficients 0.7) but showed poor agreement for categorical measures (deciles or quintiles, Cohen's kappa coefficients ≤ 0.5). Conclusion. To provide the most appropriate estimate of ambient exposure from MSWIs, it is essential that incinerator characteristics, magnitude of emissions, and surrounding meteorological and topographical conditions are considered. Reducing exposure misclassification is particularly important in environmental epidemiology to aid detection of low-level risks. © 2013 Danielle C. Ashworth et al.
Ricceri F.,Human Genetics Foundation |
Ricceri F.,University of Turin |
Matullo G.,Human Genetics Foundation |
Matullo G.,University of Turin |
And 2 more authors.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis | Year: 2012
DNA suffers from a wide range of damage, both from extracellular agents and via endogenous mechanisms. Damage of DNA can lead to cancer and other diseases. Therefore, it is plausible that sequence variants in DNA repair genes are involved in cancer development. A recent systematic review and meta-analysis, based on the " Venice criteria" , showed that out of 241 associations investigated, only three resulted to have a strong grade of cumulative evidence. These associations were: two SNPs rs1799793 and rs13181 in the ERCC2 gene and lung cancer (recessive model) and rs1805794 in the NBN gene and bladder cancer (dominant model). An update of this meta-analysis has been performed in the present paper, and we found partially inconsistent results. Inconsistencies in the literature are thus far not easy to explain. In addition, none of the cancer genome-wide association studies (GWAs) published so far showed highly statistically significant associations for any of the common DNA repair gene variants, in such a way as to place DNA repair genes among the top 10-20 hits identified in GWAs. Though this suggests that it is unlikely that DNA repair gene polymorphisms per se play a major role, a clarification of the discrepancies in the literature is needed. Also, gene/environment and gene/lifestyle interactions for the carcinogenic mechanisms involving DNA repair should be investigated more systematically and with less classification error. Finally, the combined effect of multiple SNPs in several genes in one or more relevant DNA repair pathways could have a greater impact on pathological phenotypes than SNPs in single genes, but this has been investigated only occasionally. © 2011 Elsevier B.V.
Zhang J.,Rutgers University |
Mauzerall D.L.,Princeton University |
Zhu T.,Center for Environment and Health |
Liang S.,Ohio State University |
And 2 more authors.
The Lancet | Year: 2010
Environmental risk factors, especially air and water pollution, are a major source of morbidity and mortality in China. Biomass fuel and coal are burned for cooking and heating in almost all rural and many urban households, resulting in severe indoor air pollution that contributes greatly to the burden of disease. Many communities lack access to safe drinking water and sanitation, and thus the risk of waterborne disease in many regions is high. At the same time, China is rapidly industrialising with associated increases in energy use and industrial waste. Although economic growth from industrialisation has improved health and quality of life indicators, it has also increased the release of chemical toxins into the environment and the rate of environmental disasters, with severe effects on health. Air quality in China's cities is among the worst in the world, and industrial water pollution has become a widespread health hazard. Moreover, emissions of climate-warming greenhouse gases from energy use are rapidly increasing. Global climate change will inevitably intensify China's environmental health troubles, with potentially catastrophic outcomes from major shifts in temperature and precipitation. Facing the overlap of traditional, modern, and emerging environmental dilemmas, China has committed substantial resources to environmental improvement. The country has the opportunity to address its national environmental health challenges and to assume a central role in the international effort to improve the global environment. © 2010 Elsevier Ltd. All rights reserved.