Five Glutathione S-Transferase Gene Variants in 23,452 Cases of Lung Cancer and 30,397 Controls: Meta-Analysis of 130 Studies

BACKGROUND: Glutathione S-transferases (GSTs) are known to abolish or reduce the activities of intracellular enzymes that help detoxify environmental carcinogens, such as those found in tobacco smoke. It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results. METHODS AND FINDINGS: Literature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of five GST polymorphisms ( GSTM1 null, GSTT1 null, I105V, and A114V polymorphisms in the GSTP1 genes, and GSTM3 intron 6 polymorphism) available before August, 2005, with investigation of potential sources of heterogeneity. Included in the present meta-analysis were 130 studies, involving a total of 23,452 lung cancer cases and 30,397 controls. In a combined analysis, the relative risks for lung cancer of the GSTM1 null and GSTT1 null polymorphisms were 1.18 (95% confidence interval [CI]: 1.14–1.23) and 1.09 (95% CI: 1.02–1.16), respectively, but in the larger studies they were only 1.04 (95% CI: 0.95–1.14) and 0.99 (95% CI: 0.86–1.11), respectively. In addition to size of study, ethnic background was a significant source of heterogeneity among studies of the GSTM1 null genotype, with possibly weaker associations in studies of individuals of European continental ancestry. Combined analyses of studies of the 105V, 114V, and GSTM3*B variants showed no significant overall associations with lung cancer, yielding per-allele relative risks of 1.04 (95% CI: 0.99–1.09), 1.15 (95% CI: 0.95–1.39), and 1.05 (95% CI: 0.89–1.23), respectively. CONCLUSIONS: The risk of lung cancer is not strongly associated with the I105V and A114V polymorphisms in the GSTP1 gene or with GSTM3 intron 6 polymorphism. Given the non-significant associations in the larger studies, the relevance of the weakly positive overall associations with the GSTM1 null and the GSTT1 null polymorphisms is uncertain. As lung cancer has important environmental causes, understanding any genetic contribution to it in general populations will require the conduct of particularly large and comprehensive studies

Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant

<p>Abstract</p> <p>Background</p> <p>The results of a cross-sectional study aimed to evaluate whether genetic polymorphisms (biomarkers of susceptibility) for <it>CYP1A1</it>, <it>EPHX </it>and <it>GSTM1 </it>genes that affect polycyclic aromatic hydrocarbons (PAH) activation and detoxification might influence the extent of primary DNA damage (biomarker of biologically effective dose) in PAH exposed workers are presented. PAH-exposure of the study populations was assessed by determining the concentration of 1-hydroxypyrene (1OHP) in urine samples (biomarker of exposure dose).</p> <p>Methods</p> <p>The exposed group consisted of workers (n = 109) at a graphite electrode manufacturing plant, occupationally exposed to PAH. Urinary 1OHP was measured by HPLC. Primary DNA damage was evaluated by the alkaline comet assay in peripheral blood leukocytes. Genetic polymorphisms for <it>CYP1A1</it>, <it>EPHX</it> and <it>GSTM1</it> were determined by PCR or PCR/RFLP analysis.</p> <p>Results</p> <p>1OHP and primary DNA damage were significantly higher in electrode workers compared to reference subjects. Moreover, categorization of subjects as normal or outlier highlighted an increased genotoxic risk OR = 2.59 (CI95% 1.32–5.05) associated to exposure to PAH. Polymorphisms in <it>EPHX</it> exons 3 and 4 was associated to higher urinary concentrations of 1OHP, whereas none of the genotypes analyzed (<it>CYP1A1</it>, <it>EPHX</it>, and <it>GSTM1</it>) had any significant influence on primary DNA damage as evaluated by the comet assay.</p> <p>Conclusion</p> <p>The outcomes of the present study show that molecular epidemiology approaches (i.e. cross-sectional studies of genotoxicity biomarkers) can play a role in identifying common genetic risk factors, also attempting to associate the effects with measured exposure data. Moreover, categorization of subjects as normal or outlier allowed the evaluation of the association between occupational exposure to PAH and DNA damage highlighting an increased genotoxic risk.</p

Ikan koi sebagai sumber ide penciptaan karya batik ekspresif

Keragaman corak warna berpadu dalam bentuk deformasi anatomi tubuh koi memberikan sebuah komposisi yang harmonis pada karya batik ekspresif dua dimensional.xv, 122 hal. : ill. ; 30 c

Boendeformer för asylsökanden och nyanlända, ett investeringsperspektiv på olika lösningar och dess koppling till ekonomisk integration

The number of refugees worldwide has reached record levels in recent years. Sweden experienced a sharp increase of refugees in 2015 that lead to a shortage of accommodations. The study aims to explore how the Real Estate companies view different accommodation solutions for asylum seekers and new citizens and how they view factors related to the housing with an impact on economic integration. The study is qualitative and based on interviews with the Swedish Migration Agency, and representatives of municipal and private property companies. The result is that construction of new apartments is a challenge for many municipal housing companies and several actors view long-term demand of apartments as uncertain in areas where demand has increased due to immigration. Regarding existing stock there is a lack of economic incentives to set aside apartments particularly for asylum-seekers and new citizens. There is a resistance among several actors to invest in housing particularly for asylum-seekers or new citizens. The private Real Estate companies focused on community properties does not think that housin particularly for asylum-seekers or new citizens is included in their strategy. There are municipal actors that have chosen to invest in this kind of housing. For construction of housing for asylum-seekers or new citizens to be attractive for investors it is necessary in negotiations to achieve a relatively high rent and long contractual period. It is also necessary that the location and characteristics of the housing provide good chances of alternative use once the contract expires. Regarding factors with an impact on the possibilities of economic integration the actors involvement vary. In general the municipal housing companies takes great responsibility not only for providing housing but also for creating a good living environment and in some cases even employmentAntalet flyktingar i världen har varit rekordhögt de senaste åren. Sverige upplevde en kraftig ökning av antalet asylsökande under 2015 vilket ledde till brist på boendeplatser. Studien syftar till att utforska hur fastighetsbolagen ser på olika boendelösningar för asylsökanden och nyanlända samt hur de ser på faktorer kopplade till boendet med påverkan på ekonomisk integration. Studien är kvalitativ och bygger på intervjuer med Migrationsverket samt olika representanter för kommunala och privata fastighetsbolag. Resultatet blev att nybyggnation av lägenheter är en utmaning för många kommunala bostadsbolag och flera aktörer ser långsiktiga efterfrågan på lägenheter som osäker på orter där efterfrågan ökat till följd av invandringen. Gällande befintligt bestånd saknas ekonomiska incitament att avsätta lägenheter särskilt till asylsökande och nyanlända. Det finns en ovilja bland flera aktörer att investera i särskilda boenden för asylsökanden och nyanlända. De privata fastighetsbolagen med inriktning mot samhällsfastigheter ser inte särskilda boenden för asylsökanden och nyanlända som något som ingår i deras strategi. Det finns dock kommunala aktörer som har valt att satsa på särskilda boenden. För att nybyggnation av boenden särskilt inriktade på asylsökanden eller nyanlända ska vara intressanta ur ett investeringsperspektiv krävs att man i hyresförhandlingen lyckas få en förhållandevis hög hyra och lång kontraktstid samt att boendets läge och utformning ger goda förutsättningar för alternativanvändning när hyreskontraktet löper ut. Vad gäller faktorer som påverkar möjligheterna till ekonomisk integration varierar aktörernas engagemang. Generellt tar de kommunala bostadsbolagen ett stort ansvar inte bara för att ordna tak över huvudet utan också för att skapa en god boendemiljö och i förekommande fall sysselsättning

Must Prioritarians Be Antiegalitarian?

It has been argued that Prioritarianism violates Risky Non-Antiegalitarianism, a condition stating roughly that an alternative is socially better than another if it both makes everyone better off in expectation and leads to more equality. I show that Risky Non-Antiegalitarianism is in fact compatible with Prioritarianism as ordinarily defined, but that it violates some other conditions that may be attractive to prioritarians. While I argue that the latter conditions are not core principles of Prioritarianism, the choice between these conditions and Risky Non-Antiegalitarianism nonetheless constitutes an important intramural debate for prioritarians