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| 2. |
- Cirera, Lluís, et al.
(författare)
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Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe : An Update on the EPIC Cohorts Study
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:6, s. 1089-1092
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up.METHODS: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors.RESULTS: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance.CONCLUSIONS: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems.IMPACT: The results do not support an association between education and risk of pancreatic cancer.
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| 3. |
- Barrdahl, Myrto, et al.
(författare)
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A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer : Results from the Breast and Prostate Cancer Cohort Consortium
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:6, s. 1182-1188
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom=3.05, 95%CI=1.72-5.44, Phom=1.47 × 10-4), MAST2-rs12124649 (ORhom=1.73, 95% CI =1.18-2.54, Phom=5.24 × 10-3), and INSR-rs10500204 (ORhom=1.96, 95% CI=1.44-2.67, Phom=1.68 × 10-5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom=1.78, 95% CI=1.30-2.44, Phom=3.23 × 10-4). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
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| 4. |
- Barrdahl, Myrto, et al.
(författare)
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Association of breast cancer risk loci with breast cancer survival
- 2015
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 137:12, s. 2837-2845
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Tidskriftsartikel (refereegranskat)abstract
- The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; ptrend=2.84 x 10-4; HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p2DF=1.45 x 10-3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend=6.6 x 10-4; HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p2DF=1.25 x 10-4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.
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| 6. |
- Blum, Kristin M., et al.
(författare)
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Removal of 30 active pharmaceutical ingredients in surface water under long-term artificial UV irradiation
- 2017
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 176, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the i) kinetics, and ii) proportion of photolysis of 30 relatively stable active pharmaceutical ingredients (APIs) during artificial UV irradiation for 28 d in ammonium acetate buffer, filtered and unfiltered river water. Buffer was included to control removal kinetics under stable pH conditions and without particulate matter. Dark controls were used to determine removal due to other processes than photolysis and calculate the proportion of photolysis of the total removal. The removal of each API in each matrix was determined using online solid phase extraction/liquid chromatography tandem mass spectrometry (online SPE/LC-MS/MS). Most APIs transformed during the 28 d of UV irradiation and the dark controls showed that photolysis was the major removal process for the majority of the APIs studied. The half-lives ranged from 6 h (amitriptyline) in unfiltered river water to 884 h (37 d, carbamazepine) in buffer. In unfiltered river water, the proportion of APIs with short half-lives (<48 h) was much higher (29%) than in the other matrices (4%), probably due to additional organic carbon, which could have promoted indirect photolysis. Furthermore, two APIs, memantine and fluconazole, were stable in all three matrices, while alprazolam was stable in buffer and unfiltered river water and four additional APIs were stable in buffer. Considering the relatively long-term UV-exposure, this study enabled the investigation of environmentally relevant half-lives in natural waters. Many APIs showed high persistence, which is environmentally concerning and emphasizes the importance of further studies on their environmental fate and effects.
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| 7. |
- Cunha, Sara I., et al.
(författare)
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Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer.
- 2015
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Ingår i: Cancer Research. - 1538-7445 .- 0008-5472. ; 75:12, s. 2445-2456
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Tidskriftsartikel (refereegranskat)abstract
- Exploration of new strategies for the prevention of breast cancer metastasis is justifiably at the center of clinical attention. In this study, we combined a computational biology approach with mechanism-based preclinical trials to identify inhibitors of activin-like receptor kinase (ALK) 1 as effective agents for blocking angiogenesis and metastasis in breast cancer. Pharmacologic targeting of ALK1 provided long-term therapeutic benefit in mouse models of mammary carcinoma, accompanied by strikingly reduced metastatic colonization as a monotherapy or part of combinations with chemotherapy. Gene-expression analysis of breast cancer specimens from a population-based nested case-control study encompassing 768 subjects defined endothelial expression of ALK1 as an independent and highly specific prognostic factor for metastatic manifestation, a finding that was corroborated in an independent clinical cohort. Overall, our results suggest that pharmacologic inhibition of endothelial ALK1 constitutes a tractable strategy for interfering with metastatic dissemination of breast cancer. Cancer Res; 75(12); 2445-56. ©2015 AACR.
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| 8. |
- Dimitrakopoulou, Vasiliki I., et al.
(författare)
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Interactions between genome-wide significant genetic variants and circulating concentrations of 25-Hydroxyvitamin D in relation to prostate cancer risk in the National Cancer Institute BPC3
- 2017
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 185:6, s. 452-464
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of Vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by Vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyVitamin D (25 (OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls- from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP-prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales (P ≥ 0.001). We did not find strong evidence that associations between GWASidentified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.
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| 9. |
- Fraixedas, Sara, et al.
(författare)
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Substantial decline of Northern European peatland bird populations : Consequences of drainage
- 2017
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 214, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Northern European peatlands are important habitats for biological conservation because they support rich biodiversity and unique species compositions. However, historical management of peatland habitats has had negative consequences for biodiversity and their degradation remains a major conservation concern. Despite increasing awareness of the conservation value of peatlands, the statuses and ecological requirements of peatland species have remained largely understudied. Here, we first analysed temporal trends of Northern European peatland birds to document the status of their populations using bird data from five different countries. Second, we used Finnish monitoring data to assess habitat preferences of peatland bird species, hence helping to target conservation to the most relevant habitat types. There was a general decline of 40% in Northern European peatland bird population sizes in 1981–2014 (speed of decline 1.5%/year) largely driven by Finland, where populations declined almost 50% (2.0% annual decline). In Sweden and Norway, peatland bird populations declined by 20% during 1997–2014 (1.0% annual decline). In contrast, southern populations in Estonia and Latvia, where the majority of open peatlands are protected, showed a 40% increase during 1981–2014 (1.0% annual increase). The most important habitat characteristics preferred by common peatland species in Finland were openness and low tree height, while wetness proved to be an important feature for waders. Drainage of peatlands had clear negative effects on the densities of many species, with the only exception of rustic bunting, which specializes on edge habitats. Our findings call for more effective conservation actions in Northern European peatland habitats, especially in Finland where peatland drainage represents a major threat to biodiversity.
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| 10. |
- Graham, Emily B., et al.
(författare)
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Microbes as Engines of Ecosystem Function : When Does Community Structure Enhance Predictions of Ecosystem Processes?
- 2016
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Microorganisms are vital in mediating the earth's biogeochemical cycles; yet, despite our rapidly increasing ability to explore complex environmental microbial communities, the relationship between microbial community structure and ecosystem processes remains poorly understood. Here, we address a fundamental and unanswered question in microbial ecology: 'When do we need to understand microbial community structure to accurately predict function?' We present a statistical analysis investigating the value of environmental data and microbial community structure independently and in combination for explaining rates of carbon and nitrogen cycling processes within 82 global datasets. Environmental variables were the strongest predictors of process rates but left 44% of variation unexplained on average, suggesting the potential for microbial data to increase model accuracy. Although only 29% of our datasets were significantly improved by adding information on microbial community structure, we observed improvement in models of processes mediated by narrow phylogenetic guilds via functional gene data, and conversely, improvement in models of facultative microbial processes via community diversity metrics. Our results also suggest that microbial diversity can strengthen predictions of respiration rates beyond microbial biomass parameters, as 53% of models were improved by incorporating both sets of predictors compared to 35% by microbial biomass alone. Our analysis represents the first comprehensive analysis of research examining links between microbial community structure and ecosystem function. Taken together, our results indicate that a greater understanding of microbial communities informed by ecological principles may enhance our ability to predict ecosystem process rates relative to assessments based on environmental variables and microbial physiology.
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