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| 2. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 3. |
- Canova, C., et al.
(författare)
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The influence of sensitisation to pollens and moulds on seasonal variations in asthma attacks
- 2013
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 42:4, s. 935-945
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Tidskriftsartikel (refereegranskat)abstract
- No large study has described the seasonal variation in asthma attacks in population-based asthmatics in whom sensitisation to allergen has been measured. 2637 young adults with asthma living in 15 countries reported the months in which they usually had attacks of asthma and had skin-prick tests performed. Differences in seasonal patterns by sensitisation status were assessed using generalised estimating equations. Most young adults with asthma reported periods of the year when their asthma attacks were more common (range: 47% in Sweden to 86% in Spain). Seasonal variation in asthma was not modified by sensitisation to house dust mite or cat allergens. Asthmatics sensitised to grass, birch and Alternaria allergens had different seasonal patterns to those not sensitised to each allergen, with some geographical variation. In southern Europe, those sensitised to grass allergens were more likely to report attacks occurred in spring or summer than in winter (OR March/April 2.60, 95% CI 1.70-3.97; OR May/June 4.43, 95% CI 2.34-8.39) and smaller later peaks were observed in northern Europe (OR May/June 1.25, 95% CI 0.60-2.64; OR July/August 1.66, 95% CI 0.89-3.10). Asthmatics reporting hay fever but who were not sensitised to grass showed no seasonal variations. Seasonal variations in asthma attacks in young adults are common and are different depending on sensitisation to outdoor, but not indoor, allergens.
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| 4. |
- McKay, James D., et al.
(författare)
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A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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| 5. |
- Lesseur, Corina, et al.
(författare)
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Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:12, s. 1544-1550
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
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| 7. |
- Anantharaman, Devasena, et al.
(författare)
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Combined effects of smoking and HPV16 in oropharyngeal cancer
- 2016
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:3, s. 752-761
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
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| 8. |
- Canova, C R, et al.
(författare)
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Increased prevalence of perennial allergic rhinitis in patients with obstructive sleep apnea
- 2004
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Ingår i: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 71:2, s. 138-143
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Tidskriftsartikel (refereegranskat)abstract
- Background: Impaired nasal breathing is a risk factor for obstructive sleep apnea syndrome (OSAS). Objectives: The aim of this study was to determine whether atopy to perennial allergens and existence of perennial allergic rhinitis was a risk factor for OSAS. Methods: In a case-control study, we compared the proportions of OSAS patients with atopy to perennial allergens and perennial allergic rhinitis to the proportions in patients with chronic obstructive pulmonary disease (COPD). Seventy-two OSAS patients (mean age 60.7 years; 79.4% male) and 44 COPD patients (mean age 63.6 years; 88.6% male) were selected from a hospital outpatients' clinic in Switzerland. All patients completed a respiratory symptom questionnaire, performed spirometry and had a skin prick test for atopy. Results: OSAS patients were significantly heavier than COPD patients (BMI 32.4 +/- (SD) 6.6 vs. 29.2 +/- 6.6 kg/m(2), p = 0.04) and had a better lung function than COPD patients (FEV1% predicted 91.3 +/- 19.2 vs. 51.6 +/- 18.9%, p < 0.001). Patients with OSAS were more likely to be sensitized to perennial allergens such as house dust mite (23.6 vs. 4.5%, p = 0.009) and dog (18 vs. 4.5%, p = 0.04) than the COPD patients. Perennial allergic rhinitis ( having nose problems [ nasal obstruction and/or runny nose and/or sneezing] all year and being atopic to at least one perennial allergen) was reported in 11% of OSAS patients but in only 2.3% of COPD patients (p = 0.15). Conclusion: We conclude that subjects with OSAS may have an increased risk of being allergic to perennial allergens and suffer from perennial rhinitis. Awareness of this risk may have important consideration in the clinical situation.
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| 9. |
- Canova, Moara Almeida, et al.
(författare)
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Different ecosystem services, same (dis)satisfaction with compensation : A critical comparison between farmers' perception in Scotland and Brazil
- 2019
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Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416 .- 2212-0416. ; 35, s. 164-172
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Tidskriftsartikel (refereegranskat)abstract
- Payments for Ecosystem Services (PES) schemes have increasingly expanded to consider ecosystem services (ESS). In Brazil, the Forest Code permits PES but does not specify the scheme operationalization. The way ESS should be quantified and valued has not yet been implemented country-wide, nor has the funding source for PES. Through interviews with farmers in Rio Claro-SP, Brazil, and in Cairngorms National Park in the highlands and lowlands of Scotland, UK, we compared farmers' perspectives concerning ESS and PES, focusing on the PES implementation in sugarcane landscape in Sao Paulo state. While Scottish farmers perceived more cultural services, Brazilian farmers focused on regulating services, which we attribute to socio-political and landscape differences. Despite these differences, farmers in both areas preferred opportunity cost approach for ESS valuation because this method captures efforts to maintain ESS. Thereby, the opportunity cost should be considered for valuation in PES schemes, but conversely, budgetary constraints make it impossible to satisfy farmers with PES in regions of high productivity in the southeast of Brazil. Lessons learned concerning the PES subsidies in Scotland indicates the importance of co-designing schemes with stakeholders, minimizing trade-offs between the environment. Therefore, the participants as ESS providers, beneficiaries and intermediaries in the public policies arena was recognized for co-optimize the trade-offs between costs and effectiveness in PES.
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| 10. |
- Cohen, J., et al.
(författare)
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Influence of physicians' life stances on attitudes to end-of-life decisions and actual end-of-life decision-making in six countries
- 2008
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Ingår i: Journal of Medical Ethics. - : BMJ. - 0306-6800 .- 1473-4257. ; 34:4, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine how physicians' life stances affect their attitudes to end-of-life decisions and their actual end-of-life decision-making. Methods: Practising physicians from various specialties involved in the care of dying patients in Belgium, Denmark, The Netherlands, Sweden, Switzerland and Australia received structured questionnaires on end-of-life care, which included questions about their life stance. Response rates ranged from 53% in Australia to 68% in Denmark. General attitudes, intended behaviour with respect to two hypothetical patients, and actual behaviour were compared between all large life-stance groups in each country. Results: Only small differences in life stance were found in all countries in general attitudes and intended and actual behaviour with regard to various end-of-life decisions. However, with regard to the administration of drugs explicitly intended to hasten the patient's death (PAD), physicians with specific religious affiliations had significantly less accepting attitudes, and less willingness to perform it, than non-religious physicians. They had also actually performed PAD less often. However, in most countries, both Catholics (up to 15.7% in The Netherlands) and Protestants (up to 20.4% in The Netherlands) reported ever having made such a decision. Discussion: The results suggest that religious teachings influence to some extent end-of-life decision-making, but are certainly not blankly accepted by physicians, especially when dealing with real patients and circumstances. Physicians seem to embrace religious belief in a non-imperative way, allowing adaptation to particular situations.
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