| 51. |
- Brenner, Darren R., et al.
(författare)
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Inflammatory Cytokines and Lung Cancer Risk in 3 Prospective Studies
- 2017
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Ingår i: American Journal of Epidemiology. - : OXFORD UNIV PRESS INC. - 0002-9262 .- 1476-6256. ; 185:2, s. 86-95
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Tidskriftsartikel (refereegranskat)abstract
- To further investigate the role of inflammation in lung carcinogenesis, we evaluated associations between proinflammatory cytokines and lung cancer risk. We conducted a case-control study nested within 3 prospective cohort studies-the Melbourne Collaborative Cohort Study (1990-1994), the Malm Diet and Cancer Study (1991-1996), and the Northern Sweden Health and Disease Study (initiated in 1985)-involving 807 incident lung cancer cases and 807 smoking-matched controls. Conditional logistic regression models adjusting for serum cotinine concentrations were used to estimate odds ratios for lung cancer risk associated with concentrations of interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, IL-12, interferon., tumor necrosis factor a, and granulocyte-macrophage colony-stimulating factor. We observed a higher lung cancer risk for participants with elevated concentrations of IL-6 and IL-8. These associations seemed to be stronger among former smokers (for fourth quartile vs. first quartile, odds ratio (OR) = 2.70, 95% confidence interval (CI): 1.55, 4.70) and current smokers (OR = 1.99, 95% CI: 1.15, 3.44) for IL-6 and among former smokers (OR = 2.83, 95% CI: 1.18, 6.75) and current smokers (OR = 1.30, 95% CI: 0.69, 2.44) for IL-8. No notable associations were observed among never smokers. Risk associations with IL-6 and IL-8 were observed for blood samples taken close to diagnosis (< 5 years) as well as more than 15 years postdiagnosis.
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| 52. |
- Byun, Jinyoung, et al.
(författare)
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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
- 2022
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Ingår i: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
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Tidskriftsartikel (refereegranskat)abstract
- To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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| 53. |
- Carreras-Torres, Robert, et al.
(författare)
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Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study
- 2017
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.
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| 54. |
- Carreras-Torres, Robert, et al.
(författare)
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The causal relevance of body mass index in different histological types of lung cancer : a Mendelian randomization study
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 × 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.
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| 55. |
- Chambers, Josephine M., et al.
(författare)
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Co-productive agility and four collaborative pathways to sustainability transformations
- 2022
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 72
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Tidskriftsartikel (refereegranskat)abstract
- Co-production, the collaborative weaving of research and practice by diverse societal actors, is argued to play an important role in sustainability transformations. Yet, there is still poor understanding of how to navigate the tensions that emerge in these processes. Through analyzing 32 initiatives worldwide that co-produced knowledge and action to foster sustainable social-ecological relations, we conceptualize 'co-productive agility' as an emergent feature vital for turning tensions into transformations. Co-productive agility refers to the willingness and ability of diverse actors to iteratively engage in reflexive dialogues to grow shared ideas and actions that would not have been possible from the outset. It relies on embedding knowledge production within processes of change to constantly recognize, reposition, and navigate tensions and opportunities. Co-productive agility opens up multiple pathways to transformation through: (1) elevating marginalized agendas in ways that maintain their integrity and broaden struggles for justice; (2) questioning dominant agendas by engaging with power in ways that challenge assumptions, (3) navigating conflicting agendas to actively transform interlinked paradigms, practices, and structures; (4) exploring diverse agendas to foster learning and mutual respect for a plurality of perspectives. We explore six process considerations that vary by these four pathways and provide a framework to enable agility in sustainability transformations. We argue that research and practice spend too much time closing down debate over different agendas for change - thereby avoiding, suppressing, or polarizing tensions, and call for more efforts to facilitate better interactions among different agendas.
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| 56. |
- Chambers, Josephine M., et al.
(författare)
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Six modes of co-production for sustainability
- 2021
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 4, s. 983-996
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Tidskriftsartikel (refereegranskat)abstract
- Co-production includes diverse aims, terminologies and practices. This study explores such diversity by mapping differences in how 32 initiatives from 6 continents co-produce diverse outcomes for the sustainable development of ecosystems at local to global scales. The promise of co-production to address complex sustainability challenges is compelling. Yet, co-production, the collaborative weaving of research and practice, encompasses diverse aims, terminologies and practices, with poor clarity over their implications. To explore this diversity, we systematically mapped differences in how 32 initiatives from 6 continents co-produce diverse outcomes for the sustainable development of ecosystems at local to global scales. We found variation in their purpose for utilizing co-production, understanding of power, approach to politics and pathways to impact. A cluster analysis identified six modes of co-production: (1) researching solutions; (2) empowering voices; (3) brokering power; (4) reframing power; (5) navigating differences and (6) reframing agency. No mode is ideal; each holds unique potential to achieve particular outcomes, but also poses unique challenges and risks. Our analysis provides a heuristic tool for researchers and societal actors to critically explore this diversity and effectively navigate trade-offs when co-producing sustainability.
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| 57. |
- Chen, Dan, et al.
(författare)
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A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:9, s. 2681-2688
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Tidskriftsartikel (refereegranskat)abstract
- High-risk mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas cutaneous types (e.g. HPV8 and 77) are suspected to be involved in non-melanoma skin cancer. The antibody response to HPVs is a key determinant of protective immunity, but not all infected individuals seroconvert. Genetic variability of the host may have large impact on seroconversion. A previous genome-wide association study (GWAS) has identified a susceptibility locus (rs41270488) for HPV8 seropositivity within the major histocompatibility complex (MHC) region. To further study this locus, we imputed alleles at classical leukocyte antigen (HLA) loci using HLA*IMP:02 with a reference panel from the HapMap Project and the 1958 Birth Cohort, and conducted an integrated analysis among 4811 central European subjects to assess the contribution of classical HLA alleles and gene copy number variation (CNV) at the hypervariable DRB locus within the MHC region to HPV seropositivity at both the individual HPV type level and the phylogenetic species level. Our study provides evidence that the association noted between rs41270488 and HPV8 seropositivity is driven by two independent variants, namely DQB1*0301 [odds ratio (OR) = 1.51, 95% confidence interval (CI) = 1.36-1.68, P = 1.0 x 10(-14)] and DRB1*1101 (OR = 1.89, 95% CI = 1.57-2.28, P = 1.5 x 10(-11)) within the HLA class II region. Additionally, we identified two correlated alleles DRB1*0701 (OR = 1.67, 95% CI = 1.41-1.98, P = 2.6 x 10(-9)) and DQA1*0201 (OR = 1.67, 95% CI = 1.38-1.93, P = 1.7 x 10(-8)), to be associated with HPV77 seropositivity. Comparable results were observed through imputation using SNP2HLA with another reference panel from the Type 1 diabetes Genetics Consortium. This study provides support for an important role of HLA class II alleles in antibody response to HPV infection.
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| 58. |
- Cheng, Chao, et al.
(författare)
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Mosaic chromosomal alterations are associated with increased lung cancer risk : insight from the INTEGRAL-ILCCO cohort analysis
- 2023
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. Methods: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. Results: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. Conclusions: Our study established a link between mCAs in white blood cells and increased risk of lung cancer.
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| 59. |
- Chiavaroli, Valentina, et al.
(författare)
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Exercise in pregnancy : 1-year and 7-year follow-ups of mothers and offspring after a randomized controlled trial
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- There are limited data on long-term outcomes of mothers or their offspring following exercise interventions during pregnancy. We assessed long-term effects of an exercise intervention (home-based stationary cycling) between 20-36 weeks of gestation on anthropometry and body composition in mothers and offspring after 1 and 7 years. 84 women were randomised to intervention or usual activity, with follow-up data available for 61 mother-child pairs (38 exercisers) at 1 year and 57 (33 exercisers) at 7 years. At 1 year, there were no observed differences in measured outcomes between mothers and offspring in the two groups. At the 7-year follow-up, mothers were mostly similar, except that exercisers had lower systolic blood pressure (-6.2 mmHg; p = 0.049). However, offspring of mothers who exercised during pregnancy had increased total body fat (+3.2%; p = 0.034) and greater abdominal (+4.1% android fat; p = 0.040) and gynoid (+3.5% gynoid fat; p = 0.042) adiposity compared with controls. Exercise interventions beginning during pregnancy may be beneficial to long-term maternal health. However, the initiation of exercise during pregnancy amongst sedentary mothers may be associated with adverse effects in the offspring during childhood. Larger follow-up studies are required to investigate long-term effects of exercise in pregnancy.
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| 60. |
- Christakoudi, Sofia, et al.
(författare)
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Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:10, s. 2680-2693
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.
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