| 1. |
- Attner, Bo, et al.
(författare)
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Cancer among patients with diabetes, obesity and abnormal blood lipids: a population-based register study in Sweden.
- 2012
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 23:5, s. 769-777
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study how the incidence of cancer is related to diabetes, obesity or abnormal blood lipids. METHODS: Diagnosis of diabetes, obesity or abnormal blood lipids was studied 0-10 years prior to the diagnosis of cancer in 19,756 cases of cancer and in 147,324 controls matched regarding age, sex and domicile. RESULTS: Diabetes was significantly more common prior to diagnosis in patients with liver, pancreatic, colon and urinary tract/bladder cancer and in patients with breast cancer diagnosed with diabetes 0-4 years prior to the cancer diagnosis. A lower risk of diabetes was seen in patients with prostate carcinoma among individuals with diabetes diagnosed 5-10 years prior to the cancer diagnosis. The findings remained after adjusting for obesity and high blood lipids. Obesity was significantly more common in patients with endometrial, colon and kidney cancer and with breast cancer above the age of 60 years in those where obesity was diagnosed close to the diagnosis of cancer. High blood lipids were significantly more common in patients with ovarian cancer and less common in patients with breast cancer. CONCLUSIONS: The study confirms some previous findings concerning comorbidity and cancer and highlights some new ones.
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| 3. |
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| 4. |
- Björner, Sofie, et al.
(författare)
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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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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Callaghan, Terry, et al.
(författare)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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| 6. |
- Dareng, EO, et al.
(författare)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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| 7. |
- Harbst, Katja, et al.
(författare)
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Molecular and genetic diversity in the metastatic process of melanoma.
- 2014
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 233:1, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine the molecular and genetic differences between metastatic tumours, we performed gene-expression profiling of 63 melanoma tumours obtained from 28 patients (two or three tumours/patient), followed by analysis of their mutational landscape, using targeted deep sequencing of 1697 cancer genes and DNA copy number analysis. Gene-expression signatures revealed discordant phenotypes between tumour lesions within a patient in 50% of the cases. In 18 of 22 patients (where matched normal tissue was available), we found that the multiple lesions within a patient were genetically divergent, with one or more melanoma tumours harbouring 'private' somatic mutations. In one case, the distant subcutaneous metastasis of one patient occurring 3 months after an earlier regional lymph node metastasis had acquired 37 new coding sequence mutations, including mutations in PTEN and CDH1. However, BRAF and NRAS mutations, when present in the first metastasis, were always preserved in subsequent metastases. The patterns of nucleotide substitutions found in this study indicate an influence of UV radiation but possibly also DNA alkylating agents. Our results clearly demonstrate that metastatic melanoma is a molecularly highly heterogeneous disease that continues to progress throughout its clinical course. The private aberrations observed on a background of shared aberrations within a patient provide evidence of continued evolution of individual tumours following divergence from a common parental clone, and might have implications for personalized medicine strategies in melanoma treatment. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk.
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| 8. |
- Jönsson, Göran B, et al.
(författare)
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The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.
- 2012
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Ingår i: Cancer Research. - 1538-7445. ; 72:16, s. 4028-4036
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Tidskriftsartikel (refereegranskat)abstract
- Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.
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| 9. |
- Lindqvist, Pelle G., et al.
(författare)
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Are active sun exposure habits related to lowering risk of type 2 diabetes mellitus in women, a prospective cohort study?
- 2010
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 90:1, s. 109-114
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Tidskriftsartikel (refereegranskat)abstract
- Aim An inverse relationship exists between vitamin D levels and diabetes mellitus However, little is known about the correlation of sun exposure habits and type 2 diabetes mellitus (DM) Methods A South Swedish cohort study comprising 1000 women from each age group between 25 and 64 (n = 40,000) drawn from the Southern Swedish population registry 1990-1992 At the inception of the study 74% answered the inquiry (n = 29,518) and provided detailed information on their sun exposure habits and other variables A follow-up inquiry was sent 2000-2002 which 24,098 women answered The mean follow-up time was 11 years Logistic regression analysis was used and the main outcome was the relationship between type 2 DM and sun exposure habits. Results Our findings indicated that women with active sun exposure habits were at a 30% lower risk of having DM, as compared to those with non-active habits. There was an inverse relation between this risk reduction and BMI Conclusion Our investigation gives possible epidemiological explanation to ethnic and seasonal differences in type 2 DM and metabolic control The study supports that sunlight is involved in the glucose metabolism (C) 2010 Elsevier Ireland Ltd All rights reserved.
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| 10. |
- Lindqvist, P. G., et al.
(författare)
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Avoidance of sun exposure as a risk factor for major causes of death : A competing risk analysis of the Melanoma in Southern Sweden cohort
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 375-387
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. Methods: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. Results: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. Conclusion: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.
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