| 1. |
- Beral, V., et al.
(author)
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Ovarian Cancer and Body Size : Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
- 2012
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 9:4
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Journal article (peer-reviewed)abstract
- Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade.
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| 2. |
- Beral, V., et al.
(author)
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Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
- 2012
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In: The Lancet Oncology. - 1474-5488. ; 13:9, s. 946-956
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Journal article (peer-reviewed)abstract
- Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
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| 3. |
- Björner, Sofie, et al.
(author)
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Epithelial and Stromal MicroRNA Signatures of Columnar Cell Hyperplasia Linking Let-7c to Precancerous and Cancerous Breast Cancer Cell Proliferation
- 2014
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Journal article (peer-reviewed)abstract
- Columnar cell hyperplasia (CCH) is the earliest histologically identifiable breast lesion linked to cancer progression and is characterized by increased proliferation, decreased apoptosis and elevated oestrogen receptor alpha (ER alpha) expression. The mechanisms underlying the initiation of these lesions have not been clarified but might involve early and fundamental changes in cancer progression. MiRNAs are key regulators of several biological processes, acting by influencing the post-transcriptional regulation of numerous targets, thus making miRNAs potential candidates in cancer initiation. Here we have defined novel epithelial as well as stromal miRNA signatures from columnar cell hyperplasia lesions compared to normal terminal duct lobular units by using microdissection and miRNA microarrays. Let-7c were among the identified downregulated epithelial miRNAs and its functions were delineated in unique CCH derived cells and breast cancer cell line MCF-7 suggesting anti-proliferative traits potentially due to effects on Myb and ER alpha. MiR-132 was upregulated in the stroma surrounding CCH compared to stoma surrounding normal terminal duct lobular units (TDLUs), and overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co-cultured with epithelial CCH cells caused substantial expression changes of genes involved in metabolism, DNA damage and cell motility. The miRNA signatures identified in CCH indicate early changes in the epithelial and stromal compartment of CCH and could represent early key alterations in breast cancer progression that potentially could be targeted in novel prevention or treatment schedules.
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| 4. |
- Dalgaard, C. J., et al.
(author)
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Why Are Rich Countries More Politically Cohesive?
- 2013
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In: Scandinavian Journal of Economics. - : Wiley. - 0347-0520. ; 115:2, s. 423-448
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Journal article (peer-reviewed)abstract
- We document empirically that rich countries are more politically cohesive than poorer countries. In order to explain this regularity, we provide a model where political cohesion is linked to the emergence of a fully functioning market economy. Without market exchange, the welfare of inherently selfish individuals will be mutually independent. Whoever has greater bargaining power will be willing to make decisions that enhance the productivity of their supporters at the expense of other groups in society. If the gains from specialization are sufficiently large, however, a market economy will emerge. From being essentially non-cohesive under self-sufficiency, the political decision-making process becomes cohesive in the market economy, because the welfare of individuals will be mutually interdependent as a result of the exchange of goods.
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| 5. |
- Demenais, F, et al.
(author)
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Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study.
- 2010
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 1568-1583
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Journal article (peer-reviewed)abstract
- Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P ≤ .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
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| 6. |
- Hov, J. R., et al.
(author)
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Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis
- 2011
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In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 53:6, s. 1967-1976
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Journal article (peer-reviewed)abstract
- The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 x 10(-32) and P = 1.8 x 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DR beta chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;53:1967-1976)
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| 7. |
- Månsson, Kristoffer, et al.
(author)
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Predicting Long-Term Outcome of Cognitive Behaviour Therapy for Social Anxiety Disorder Using fMRI and Support Vector Machiness
- 2014
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In: Abstracts from the 44th Congress of the European Association for Behavioural & Cognitive Therapies.
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Conference paper (peer-reviewed)abstract
- Background: Cognitive behavioural therapy (CBT) has yielded robust treatment effects for social anxiety disorder (SAD) but still many patients do not respond fully to treatment, and a substantial proportion relapse after treatment has ended. Identification of robust predictors of sustained treatment responses could be of high clinical importance.Methods: We used functional magnetic resonance imaging (fMRI; 3T General Electric) to assess 26 patients (85% women, mean age 32.3 years) with SAD. Blood-oxygen-level dependent (BOLD) responses to self-referential criticism, i.e. reading sentences such as "Nobody likes you" were compared to criticism referring to other individuals. Responses in the fear network, i.e. the amygdala, hippocampus, anterior cingulate cortex (ACC), and insula, were evaluated in a Support Vector Machine (SVM) approach to predict treatment outcome one-year after Internet-delivered CBT. We applied leave-one-out cross-validation to increase the generalizability of the data.Results: At one-year follow-up, three patients had dropped out. Twelve (52%) of the assessed patients met the response criteria, i.e. very much or much improved according to the Clinical Global Impression-Improvement scale (CGI-I). SVM on initial BOLD response, accurately classified patients according to responder status, based on multi-voxel patterns in the ACC (balanced accuracy of 91.7%, p=.001), and the ACC together with the amygdala (83.0%, p=.004) as well as the hippocampus (73.9%,p=.032).Conclusions: We demonstrate that initial multi-voxel BOLD response patterns to self-referential criticism in the ACC, amygdala, and hippocampus are highly predictive of long-term improvement of CBT in patients with SAD.
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